{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:19:29Z","timestamp":1787030369526,"version":"build-2736575974"},"reference-count":47,"publisher":"Baishideng Publishing Group Inc.","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n                  <jats:p>Bortezomib (BTZ) is ineffective in gastric carcinoma (GC) due to lysosome-mediated resistance. Wogonin derivative V8 targets lysosomes.<\/jats:p>\n                  <jats:p>AIM<\/jats:p>\n                  <jats:p>To address the limited efficacy of BTZ in GC and explore whether wogonin derivative V8 enhances anti-GC effects by overcoming lysosome-mediated resistance.<\/jats:p>\n                  <jats:p>METHODS<\/jats:p>\n                  <jats:p>In vitro  experiments used four human GC cell lines (MGC-803, BGC-823, AGS, and HGC-27) to assess cell viability (cell counting kit-8), lysosomal function (LysoSensor staining), autophagy (western blotting for light chain 3\/p62), and drug synergy [combination index (CI)]. Liquid chromatography\/mass spectrometry measured intracellular BTZ concentration. Transcription factor EB (TFEB), a master regulator of lysosomal and autophagy genes, was investigated using small interfering RNA silencing and plasmid overexpression. In vivo  efficacy\/safety was tested in MGC-803 xenograft nude mice, and patient-derived tumor organoids (PDOs) validated clinical relevance.<\/jats:p>\n                  <jats:p>RESULTS<\/jats:p>\n                  <jats:p>BTZ was trapped in GC cell lysosomes, reducing its proteasome accessibility and inducing resistance; lysosome number correlated positively with the half-maximal inhibitory concentration of BTZ. V8 induced lysosomal damage\/deacidification, increasing intracellular BTZ availability. V8 + BTZ synergistically inhibited GC cell growth (CI &lt; 1), upregulated proteotoxic stress markers (ATF4 , immunoglobulin heavy chain binding protein) and apoptotic mediators (cleaved caspase-3). TFEB knockdown enhanced V8 + BTZ cytotoxicity, whereas its overexpression reduced cell death, indicating a protective role of TFEB in gastric cancer cells. In xenografts, V8 + BTZ significantly reduced tumor volume\/weight (P  &lt; 0.01) without organ toxicity. PDOs showed enhanced sensitivity to V8 + BTZ vs  monotherapy.<\/jats:p>\n                  <jats:p>CONCLUSION<\/jats:p>\n                  <jats:p>Lysosomes mediate BTZ resistance in GC; V8 overcomes this by disrupting lysosomes, enabling BTZ to target proteasomes. V8 + BTZ is a safe, effective strategy against GC.<\/jats:p>","DOI":"10.3748\/wjg.v32.i8.113299","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:45:52Z","timestamp":1770695152000},"source":"Crossref","is-referenced-by-count":1,"title":["Wogonin derivative V8 enhances bortezomib efficacy in gastric carcinoma by disrupting lysosome-mediated drug resistance"],"prefix":"10.3748","volume":"32","author":[{"given":"Si-Chan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Zi","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Tao","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Bin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Long","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-Yong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09925-3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9474-7"},{"key":"B3","unstructured":"Wang H, Cao Q, Dudek AZ. 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