{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:27:27Z","timestamp":1787740047421,"version":"build-2784847793"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fujian Health and Education joint project","award":["2019-WJ-37"],"award-info":[{"award-number":["2019-WJ-37"]}]},{"name":"Fujian Health and Education joint project","award":["2018 J01400"],"award-info":[{"award-number":["2018 J01400"]}]},{"name":"Fujian Health and Education joint project","award":["JCYJ20210324121802008"],"award-info":[{"award-number":["JCYJ20210324121802008"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2019-WJ-37"],"award-info":[{"award-number":["2019-WJ-37"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2018 J01400"],"award-info":[{"award-number":["2018 J01400"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["JCYJ20210324121802008"],"award-info":[{"award-number":["JCYJ20210324121802008"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Program","award":["2019-WJ-37"],"award-info":[{"award-number":["2019-WJ-37"]}]},{"name":"Shenzhen Science and Technology Program","award":["2018 J01400"],"award-info":[{"award-number":["2018 J01400"]}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20210324121802008"],"award-info":[{"award-number":["JCYJ20210324121802008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Antiangiogenic therapy is an important treatment strategy for metastatic colorectal cancer (mCRC). We carried out a clinical study of low-dose apatinib (250 mg) monotherapy as a third-line treatment in patients with mCRC and assessed its efficacy and safety. It demonstrated that low-dose apatinib had comparable survival outcomes, significantly improved the patient quality of life, and caused tolerable adverse reactions. To further investigate the underlying mechanism of the effects of apatinib in CRC besides angiogenesis, we performed RNA-seq, and our results suggested that apatinib may have other potential antitumor mechanisms in CRC through multiple pathways, including exosomes secretion. In RKO and HCT116 cells, apatinib significantly reduced exosomes secretion by targeting multivesicular body (MVB) transport. Further studies have indicated that apatinib not only promoted the degradation of MVBs via the regulation of LAMP2 but also interfered with MVB transport by inhibiting Rab11 expression. Moreover, apatinib inhibited MVB membrane fusion by reducing SNAP23 and VAMP2 expression. In vivo, apatinib inhibited orthotopic murine colon cancer growth and metastasis and reduced the serum exosomes amount. This novel regulatory mechanism provides a new perspective for the antitumor effect of apatinib beyond angiogenesis inhibition.<\/jats:p>","DOI":"10.3390\/cancers14102492","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T12:25:57Z","timestamp":1652963157000},"page":"2492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Studies of the Efficacy of Low-Dose Apatinib Monotherapy as Third-Line Treatment in Patients with Metastatic Colorectal Cancer and Apatinib\u2019s Novel Anticancer Effect by Inhibiting Tumor-Derived Exosome Secretion"],"prefix":"10.3390","volume":"14","author":[{"given":"Lingying","family":"Zhao","sequence":"first","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyi","family":"Gao","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhou","family":"Xiang","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Feng","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runyang","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-4136","authenticated-orcid":false,"given":"Xiaoting","family":"Hong","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-yan","family":"Zhan","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xiao","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"},{"name":"Department of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3998-5145","authenticated-orcid":false,"given":"Tianhui","family":"Hu","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, Xiamen University School of Medicine, Xiamen 361102, China"},{"name":"Shenzhen Research Institute of Xiamen University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.canlet.2021.09.034","article-title":"Incidence, mortality, survival, risk factor and screening of colorectal cancer: A comparison among China, Europe, and northern America","volume":"522","author":"Li","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.cgh.2020.07.028","article-title":"Screening History and Comorbidities Help Refine Stop Ages for Colorectal Cancer Screening","volume":"19","author":"Calderwood","year":"2021","journal-title":"Clin. 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