{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:04:15Z","timestamp":1793419455093,"version":"4.5.0"},"reference-count":67,"publisher":"American Chemical Society (ACS)","issue":"40","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Lietuvos Mokslo Taryba","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020275","name":"Vilnius University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Berberine, a natural isoquinoline alkaloid derived fromCoptidis rhizoma has long been used in traditional medicine and has recently attracted attention for its potential role in cancer therapy. Emerging evidence suggests that berberine can inhibit proprotein convertase subtilisin\/kexin type 9 (PCSK9), a key regulator of lipid metabolism that has also been implicated in tumor biology. While the role of PCSK9 in cardiovascular diseases is well established, its contribution to cancer progression and therapeutic response remains incompletely understood. Here, we investigated whether berberine-mediated inhibition of PCSK9 could enhance the efficacy of chemotherapeutic agents. Berberine reduced PCSK9 expression at both mRNA and protein levels and increased LDLR abundance in A431 cells, which exhibit high basal PCSK9 expression. Functionally, berberine decreased cell viability in a dose-dependent manner and exhibited a strong synergistic interaction with etoposide, according to the HSA synergy score. Mechanistic analyses indicated that berberine enhances etoposide-induced cytotoxicity, at least in part by delaying the resolution of DNA-damage associated signals. Importantly, genetic silencing of PCSK9 recapitulated the sensitizing effect of berberine, while palmatine, a structurally related compound with lower efficacy in reducing PCSK9 levels, showed decreased synergy with etoposide, although evaluated under a different range of concentrations. Collectively, these findings support a role for PCSK9 in modulating cellular sensitivity to etoposide and suggest that berberine may act as a potential adjuvant in this context.<\/jats:p>","DOI":"10.1021\/acsomega.6c06421","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:01:28Z","timestamp":1790924488000},"page":"61344-61357","source":"Crossref","is-referenced-by-count":1,"title":["Berberine and Etoposide Exert Synergistic Anticancer\nEffects in A431 Epidermoid Carcinoma Cells"],"prefix":"10.1021","volume":"11","author":[{"given":"Zeynep O\u0308zlem","family":"Cinar","sequence":"first","affiliation":[{"name":"Vilnius University , , ,","place":["Vilnius, Lithuania, LT-10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerija","family":"S\u030catrova","sequence":"additional","affiliation":[{"name":"Vilnius University , , ,","place":["Vilnius, Lithuania, LT-10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay Kumar","family":"Vijaya","sequence":"additional","affiliation":[{"name":"Vilnius University , , ,","place":["Vilnius, Lithuania, LT-10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milda","family":"Babonaite\u0307-Aleksieju\u0305ne\u0307","sequence":"additional","affiliation":[{"name":"Vilnius University , , ,","place":["Vilnius, Lithuania, LT-10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goda","family":"Glebavic\u030ciu\u0305te\u0307","sequence":"additional","affiliation":[{"name":"Vilnius University , , ,","place":["Vilnius, Lithuania, LT-10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelijus","family":"Burokas","sequence":"additional","affiliation":[{"name":"Vilnius University , , ,","place":["Vilnius, Lithuania, LT-10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-4698","authenticated-orcid":true,"given":"Giulio","family":"Preta","sequence":"additional","affiliation":[{"name":"Vilnius University , , ,","place":["Vilnius, Lithuania, LT-10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"2026101315071253800_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111758","article-title":"PCSK9 and cancer: Rethinking the\nlink","volume":"140","author":"Mahboobnia","year":"2021","journal-title":"Biomed. Pharmacother."},{"issue":"6","key":"2026101315071253800_cit2","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1161\/01.ATV.4.6.604","article-title":"Contribution of the\nreceptor pathway to low density lipoprotein catabolism in humans.\nNew methods for quantitation","volume":"4","author":"Slater","year":"1984","journal-title":"Arteriosclerosis"},{"issue":"2","key":"2026101315071253800_cit3","first-page":"219","article-title":"The role of cholesterol\nmetabolism in cancer","volume":"9","author":"Ding","year":"2019","journal-title":"Am. J. Cancer Res."},{"issue":"10","key":"2026101315071253800_cit4","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.32604\/or.2024.047933","article-title":"The role of cholesterol\nmetabolism in lung cancer","volume":"32","author":"Xiu","year":"2024","journal-title":"Oncol. Res."},{"issue":"2","key":"2026101315071253800_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2024.159578","article-title":"Cholesterol metabolism\nin pancreatic cancer and associated therapeutic strategies","volume":"1870","author":"Daya","year":"2025","journal-title":"Biochim. Biophys. Acta, Mol. Cell Biol. Lipids"},{"key":"2026101315071253800_cit6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.116802","article-title":"Cholesterol\nmetabolism in tumor immunity: Mechanisms and therapeutic opportunities\nfor cancer","volume":"234","author":"Guo","year":"2025","journal-title":"Biochem. Pharmacol."},{"issue":"10","key":"2026101315071253800_cit7","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1194\/jlr.M018093","article-title":"Role of\nthe C-terminal domain of\nPCSK9 in degradation of the LDL receptors","volume":"52","author":"Holla","year":"2011","journal-title":"J.\nLipid Res."},{"issue":"1","key":"2026101315071253800_cit8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1042\/BJ20130930","article-title":"PCSK9 acts as a chaperone for the\nLDL receptor in the endoplasmic reticulum","volume":"457","author":"Str\u00f8m","year":"2014","journal-title":"Biochem.\nJ."},{"issue":"6","key":"2026101315071253800_cit9","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1093\/hmg\/ddr578","article-title":"Interaction between the ligand-binding\ndomain of the LDL receptor and the C-terminal domain of PCSK9 is required\nfor PCSK9 to remain bound to the LDL receptor during endosomal acidification","volume":"21","author":"Tveten","year":"2012","journal-title":"Hum. Mol. Genet."},{"issue":"2","key":"2026101315071253800_cit10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2174\/0929867330666230228120601","article-title":"Efficacy and Safety of Alirocumab\nand Evolocumab as Proprotein Convertase Subtilisin\/Kexin Type 9 (PCSK9)\nInhibitors in Familial Hypercholesterolemia: A Systematic Review and\nMeta-Analysis","volume":"31","author":"Ghasempour","year":"2024","journal-title":"Curr. Med. Chem."},{"issue":"6","key":"2026101315071253800_cit11","doi-asserted-by":"publisher","first-page":"641","DOI":"10.18553\/jmcp.2016.22.6.641","article-title":"A Systematic Review\nof PCSK9 Inhibitors Alirocumab and Evolocumab","volume":"22","author":"McDonagh","year":"2016","journal-title":"J. Managed Care Spec. Pharm."},{"issue":"16","key":"2026101315071253800_cit12","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1056\/NEJMoa1912387","article-title":"Two Phase\n3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol","volume":"382","author":"Ray","year":"2020","journal-title":"N. Engl. J. Med."},{"issue":"4","key":"2026101315071253800_cit13","doi-asserted-by":"publisher","DOI":"10.3390\/ph16040577","article-title":"Inclisiran,\nLow-Density Lipoprotein Cholesterol and Lipoprotein (a)","volume":"16","author":"Katsiki","year":"2023","journal-title":"Pharmaceuticals"},{"issue":"4","key":"2026101315071253800_cit14","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.bbrc.2007.08.060","article-title":"Berberine-induced\nLDLR up-regulation involves JNK pathway","volume":"362","author":"Lee","year":"2007","journal-title":"Biochem.\nBiophys. Res. Commun."},{"issue":"42","key":"2026101315071253800_cit15","doi-asserted-by":"publisher","first-page":"28885","DOI":"10.1074\/jbc.M109.052407","article-title":"Hepatocyte nuclear\nfactor 1alpha plays a critical role in PCSK9 gene\ntranscription and regulation by the natural hypocholesterolemic compound\nberberine","volume":"284","author":"Li","year":"2009","journal-title":"J. Biol. Chem."},{"issue":"7","key":"2026101315071253800_cit16","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1142\/S0192415X15500846","article-title":"Berberine\nIncreases Doxorubicin Sensitivity\nby Suppressing STAT3 in Lung Cancer","volume":"43","author":"Zhu","year":"2015","journal-title":"Am. J.\nChin. Med."},{"issue":"6","key":"2026101315071253800_cit17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021416","article-title":"Berberine inhibits human hepatoma cell invasion without cytotoxicity\nin healthy hepatocytes","volume":"6","author":"Liu","year":"2011","journal-title":"PLoS One"},{"issue":"1","key":"2026101315071253800_cit18","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2024.114094","article-title":"Berberine\nincreases the killing effect of pirarubicin on HCC cells by inhibiting\nATG4B-autophagy pathway","volume":"439","author":"He","year":"2024","journal-title":"Exp. Cell Res."},{"issue":"6","key":"2026101315071253800_cit19","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26061666","article-title":"Berberine\nand Cisplatin Exhibit Synergistic Anticancer Effects on\nOsteosarcoma MG-63 Cells by Inhibiting the MAPK Pathway","volume":"26","author":"Gao","year":"2021","journal-title":"Molecules"},{"key":"2026101315071253800_cit20","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.616251","article-title":"Berberine\nImproves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis\nand Repressing PI3K\/AKT\/mTOR Signaling Pathway in Gastric Cancer","volume":"11","author":"Kou","year":"2020","journal-title":"Front. Pharmacol."},{"issue":"7","key":"2026101315071253800_cit21","doi-asserted-by":"publisher","first-page":"5697","DOI":"10.1007\/s11033-023-08381-w","article-title":"Berberine\ninhibits the progression of renal cell carcinoma\ncells by regulating reactive oxygen species generation and inducing\nDNA damage","volume":"50","author":"Zhao","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"2026101315071253800_cit22","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2025.110481","article-title":"Berberine\ntriggers apoptosis through the PI3K\/Akt pathways\nand Nrf2 by inducing ROS in papillary thyroid cancer","volume":"771","author":"Li","year":"2025","journal-title":"Arch. Biochem. Biophys."},{"key":"2026101315071253800_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118147","article-title":"Berberine\npromotes\napoptosis and inhibits the migration of oral squamous carcinoma cells\nthrough inhibition of the RAGE\/PI3K\/AKT\/mTOR pathway","volume":"187","author":"Liu","year":"2025","journal-title":"Biomed. Pharmacother."},{"issue":"6","key":"2026101315071253800_cit24","doi-asserted-by":"publisher","first-page":"4139","DOI":"10.3892\/mmr.2017.6513","article-title":"Berberine\nactivates\nAMPK to suppress proteolytic processing, nuclear translocation and\ntarget DNA binding of SREBP-1c in 3T3-L1 adipocytes","volume":"15","author":"Jang","year":"2017","journal-title":"Mol. Med. Rep."},{"issue":"1","key":"2026101315071253800_cit25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23780-x","article-title":"Involvement\nof AMP-activated protein\nkinase and Death Receptor 5 in TRAIL-Berberine-induced apoptosis of\ncancer cells","volume":"8","author":"Ke","year":"2018","journal-title":"Sci. Rep."},{"issue":"8","key":"2026101315071253800_cit26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa102","article-title":"SynergyFinder: a web application\nfor analyzing drug combination dose-response matrix data","volume":"36","author":"Ianevski","year":"2020","journal-title":"Bioinformatics"},{"issue":"W1","key":"2026101315071253800_cit27","doi-asserted-by":"publisher","first-page":"W488","DOI":"10.1093\/nar\/gkaa216","article-title":"SynergyFinder\n2.0: visual analytics\nof multi-drug combination synergies","volume":"48","author":"Ianevski","year":"2020","journal-title":"Nucleic\nAcids Res."},{"issue":"4","key":"2026101315071253800_cit28","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.bbrc.2012.08.091","article-title":"Berberine inhibits human colon cancer cell migration\nvia AMP-activated protein kinase-mediated downregulation of integrin\nbeta1 signaling","volume":"426","author":"Park","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"9","key":"2026101315071253800_cit29","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28093823","article-title":"Berberine Inhibited Growth and Migration of Human Colon\nCancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting\nAquaporins 1, 3 and 5 Expressions","volume":"28","author":"Tarawneh","year":"2023","journal-title":"Molecules"},{"issue":"1","key":"2026101315071253800_cit30","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/1440-1681.13582","article-title":"Berberine\ninhibits\nnon-small cell lung cancer cell growth through repressing DNA repair\nand replication rather than through apoptosis","volume":"49","author":"Ni","year":"2022","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"issue":"10","key":"2026101315071253800_cit31","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.471","article-title":"Berberine\ninduces oxidative DNA damage and impairs homologous recombination\nrepair in ovarian cancer cells to confer increased sensitivity to\nPARP inhibition","volume":"8","author":"Hou","year":"2017","journal-title":"Cell Death Dis."},{"key":"2026101315071253800_cit32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.104994","article-title":"Structure-activity\nrelationship and\nbiological evaluation of berberine derivatives as PCSK9 down-regulating\nagents","volume":"113","author":"Fan","year":"2021","journal-title":"Bioorg. Chem."},{"issue":"7839","key":"2026101315071253800_cit33","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41586-020-2911-7","article-title":"Inhibition of PCSK9\npotentiates immune checkpoint therapy for cancer","volume":"588","author":"Liu","year":"2020","journal-title":"Nature"},{"issue":"4","key":"2026101315071253800_cit34","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1007\/s13238-021-00821-2","article-title":"Potentiating CD8(+) T cell antitumor activity by inhibiting\nPCSK9\nto promote LDLR-mediated TCR recycling and signaling","volume":"12","author":"Yuan","year":"2021","journal-title":"Protein Cell"},{"key":"2026101315071253800_cit35","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1134063","article-title":"Identification and validation of\nPCSK9 as a prognostic\nand immune-related influencing factor in tumorigenesis: a pan-cancer\nanalysis","volume":"13","author":"Sun","year":"2023","journal-title":"Front. Oncol."},{"issue":"2","key":"2026101315071253800_cit36","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.atherosclerosis.2008.02.004","article-title":"Berberine\ndecreases PCSK9 expression in HepG2 cells","volume":"201","author":"Cameron","year":"2008","journal-title":"Atherosclerosis"},{"key":"2026101315071253800_cit37","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/2337818","article-title":"Berberine Suppresses\nEMT in Liver and Gastric Carcinoma Cells through Combination with\nTGFR Regulating TGF-\/Smad Pathway","volume":"2021","author":"Du","year":"2021","journal-title":"Oxid. Med.\nCell. Longevity"},{"issue":"3","key":"2026101315071253800_cit38","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28030991","article-title":"13-Butoxyberberine Bromide Inhibits\nMigration and Invasion\nin Skin Cancer A431 Cells","volume":"28","author":"Laomethakorn","year":"2023","journal-title":"Molecules"},{"issue":"1","key":"2026101315071253800_cit39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34237-6","article-title":"Triciribine increases\nLDLR expression\nand LDL uptake through stabilization of LDLR mRNA","volume":"8","author":"Bjune","year":"2018","journal-title":"Sci. Rep."},{"key":"2026101315071253800_cit40","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.mrfmmm.2015.01.007","article-title":"Anthracyclines induce double-strand\nDNA breaks at active gene promoters","volume":"773","author":"Yang","year":"2015","journal-title":"Mutat.\nRes., Fundam. Mol. Mech. Mutagen."},{"issue":"12","key":"2026101315071253800_cit41","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022110632","article-title":"Topoisomerase II poisons inhibit vertebrate DNA replication\nthrough distinct mechanisms","volume":"41","author":"Van Ravenstein","year":"2022","journal-title":"EMBO J."},{"key":"2026101315071253800_cit42","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.canlet.2021.08.006","article-title":"Inhibition\nof the DSB repair protein RAD51 potentiates the cytotoxic efficacy\nof doxorubicin via promoting apoptosis-related death pathways","volume":"520","author":"Schu\u0308rmann","year":"2021","journal-title":"Cancer Lett."},{"issue":"12","key":"2026101315071253800_cit43","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1221-6","article-title":"Combination of chemotherapy and physical plasma elicits\nmelanoma cell death via upregulation of SLC22A16","volume":"9","author":"Sagwal","year":"2018","journal-title":"Cell Death Dis."},{"issue":"3","key":"2026101315071253800_cit44","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.bbagen.2017.11.019","article-title":"Macrovipecetin, a C-type lectin from Macrovipera\nlebetina venom, inhibits proliferation migration and invasion of SK-MEL-28\nhuman melanoma cells and enhances their sensitivity to cisplatin","volume":"1862","author":"Hammouda","year":"2018","journal-title":"Biochim. Biophys. Acta, Gen. Subj."},{"issue":"5","key":"2026101315071253800_cit45","doi-asserted-by":"publisher","first-page":"318","DOI":"10.7326\/M18-2753","article-title":"Lipophilic\nStatins and Risk for Hepatocellular Carcinoma and Death in Patients\nWith Chronic Viral Hepatitis: Results From a Nationwide Swedish Population","volume":"171","author":"Simon","year":"2019","journal-title":"Ann. Intern. Med."},{"issue":"9","key":"2026101315071253800_cit46","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41569-024-01017-x","article-title":"Cardiovascular disease\nand cancer: shared risk factors and mechanisms","volume":"21","author":"Wilcox","year":"2024","journal-title":"Nat. Rev. Cardiol."},{"key":"2026101315071253800_cit47","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.727487","article-title":"Cardio-Oncology:\nA Myriad of Relationships Between Cardiovascular Disease and Cancer","volume":"9","author":"Wang","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"issue":"3","key":"2026101315071253800_cit48","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1038\/s41440-024-02015-9","article-title":"The interplay\nbetween cancer and cardiovascular disease","volume":"48","author":"Kuwabara","year":"2025","journal-title":"Hypertens.\nRes."},{"key":"2026101315071253800_cit49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175721","article-title":"The evolving landscape of PCSK9 inhibition\nin cancer","volume":"949","author":"Oza","year":"2023","journal-title":"Eur. J. Pharmacol."},{"issue":"20","key":"2026101315071253800_cit50","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408514","article-title":"PCSK9 Promotes\nthe Malignancy of Triple-negative Breast\nCancer Cells by Reducing Cholesterol Levels at the Plasma Membrane\nto Activate EGFR and HER3","volume":"12","author":"Li","year":"2025","journal-title":"Adv. Sci."},{"issue":"1","key":"2026101315071253800_cit51","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-021-00218-1","article-title":"PCSK9 promotes\ntumor growth by inhibiting\ntumor cell apoptosis in hepatocellular carcinoma","volume":"10","author":"Zhang","year":"2021","journal-title":"Exp. Hematol. Oncol."},{"key":"2026101315071253800_cit52","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.609663","article-title":"Proprotein Convertase Subtilisin\/Kexin\nType 9 Promotes Gastric Cancer\nMetastasis and Suppresses Apoptosis by Facilitating MAPK Signaling\nPathway Through HSP70 Up-Regulation","volume":"10","author":"Xu","year":"2020","journal-title":"Front.\nOncol."},{"issue":"1","key":"2026101315071253800_cit53","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02477-0","article-title":"PCSK9 promotes the\nprogression and metastasis of colon cancer cells through regulation\nof EMT and PI3K\/AKT signaling in tumor cells and phenotypic polarization\nof macrophages","volume":"41","author":"Wang","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"issue":"3","key":"2026101315071253800_cit54","first-page":"2787","article-title":"PCSK9 regulates\napoptosis in human neuroglioma u251 cells via mitochondrial signaling\npathways","volume":"8","author":"Piao","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"issue":"5","key":"2026101315071253800_cit55","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.3892\/etm.2017.4218","article-title":"PCSK9 regulates\napoptosis in human lung adenocarcinoma A549 cells via endoplasmic\nreticulum stress and mitochondrial signaling pathways","volume":"13","author":"Xu","year":"2017","journal-title":"Exp. Ther. Med."},{"issue":"1","key":"2026101315071253800_cit56","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-019-0243-6","article-title":"Berberine in combination\nwith cisplatin induces necroptosis and apoptosis\nin ovarian cancer cells","volume":"52","author":"Liu","year":"2019","journal-title":"Biol. 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