title: Vasohibin 2 decreases the cisplatin sensitivity of hepatocarcinoma cell line by downregulating p53.
abstract: Hepatocellular carcinoma (HCC) is a prevalent problem worldwide. Chemotherapy, especially cisplatin (CDDP)-based systemic chemotherapy, is the best option for advanced liver cancer. However, CDDP resistance is becoming common and hindering the clinical application of CDDP. Meanwhile, no consensus has been reached regarding the chemotherapeutic use of vasohibin 2 (VASH2), which promotes the angiogenesis and proliferation of cancer cells. In this work, a tissue microarray was used to observe VASH2 and its possible role in cancer treatment. Results showed that VASH2 was highly expressed in HCC tissues and was significantly correlated with cancer differentiation. To further investigate the efficacy and mechanism of the combination of VASH2 with anti-cancer drugs in liver cancer cells, we stably built VASH2 overexpression and knockdown cell lines. We found that VASH2 can influence the CDDP sensitivity and that the cell overexpression of VASH2 had a higher cell viability and lower apoptosis rate after CDDP exposure. We also observed that VASH2 overexpression downregulated wild-type p53, as well as suppressed the expression of the pro-apoptotic protein BCL2-associated X protein (Bax) and cleaved caspase-3 (CC-3) after treatment by CDDP. Conversely, the knockdown of VASH2 significantly inhibited these effects. In an in vivo chemosensitivity study, nude mice were subcutaneously injected with tumor cells and received CDDP treatment through intraperitoneal administration every 3 days. We found that VASH2 knockdown markedly limited the tumor growth and enhanced the CDDP toxicity and apoptosis of tumor cells. Western blot analysis revealed that tumor cells with downregulated VASH2 had a higher expression of wild-type p53, Bax, and CC-3 than control cells. Overall, our results indicated the novel roles of VASH2 in the chemoresistance of hepatocarcinoma cells to CDDP and suggested that VASH2 may be a promising anticancer target.
authors.affiliation: Laboratory of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of Endocrinology, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of General Surgery, Taicang City First People's Hospital, Suzhou, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Suzhou University, Suzhou, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of General Surgery, Fuyang People's Hospital, Fuyang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Laboratory of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhuyin
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D003710:Demography; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D016159:Tumor Suppressor Protein p53; C574858:VASH2 protein, human; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D002945:Cisplatin