title: Galectin-3 inhibition sensitizes human renal cell carcinoma cells to arsenic trioxide treatment.
abstract: The anti-tumor effects of arsenic trioxide (ATO) were well established in acute promyelocytic leukemia, but not in renal cell carcinoma (RCC). Recent evidences indicate that galectin-3 (Gal-3) plays an anti-apoptotic role in chemotherapy induced tumor cell death. This study was intended to clarify the exact roles of Gal-3 performed in ATO-induced apoptosis in RCC cells. Weak apoptosis was observed in Gal-3-positive RCC cells (Caki-1, Caki-2, 786-0, and ACHN) following ATO treatment. However, ATO treatment upregulated Gal-3 expression concurrently caused a Synexin-cooperated translocation of Gal-3 from the nucleus to the cytoplasm. Gal-3-knockdown cells were more sensitive to ATO treatment as indicated by a strong mitochondria-dependent apoptosis following ATO treatment. Meanwhile, Gal-3 was found to inhibit ATO-induced apoptosis through enhancing Bcl-2 expression and stabilizing mitochondria. To confirm the results obtained from genetic method, we employed a Gal-3 inhibitor, modified citrus prectin (MCP), and co-treated the RCC cells with ATO. The cells showed an increased apoptosis in the syngeneic application of Gal-3 inhibition and ATO compared with ATO application alone. Based on these results, we conclude that Gal-3 inhibition sensitizes human renal cell carcinoma cells to ATO treatment through increasing mitochondria-dependent apoptosis. Our studies implicate synergetic application of ATO and Gal-3 inhibition as a potential strategy for RCC treatment.
authors.affiliation: Department of Urological Surgery; The Affiliated Tumor Hospital of Harbin Medical University; Heilongjian, P.R. China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.forename: Mancheng
authors.initials: M
authors.lastname: Gong
authors.forename: Guiying
authors.initials: G
authors.lastname: Guo
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Han
authors.forename: Ruihua
authors.initials: R
authors.lastname: An
mesh_terms: D017310:Annexin A7 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007680:Kidney Neoplasms; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology*; D010368:Pectins / Q000494:pharmacology*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D017310:Annexin A7; D000970:Antineoplastic Agents; D001152:Arsenicals; D037502:Galectin 3; D010087:Oxides; D034741:RNA, Small Interfering; D010368:Pectins; D000077237:Arsenic Trioxide
keywords: apoptosis; arsenic trioxide; galectin-3; mitochondria; renal cell carcinoma
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