title: Sorafenib reverses resistance of gastric cancer to treatment by cisplatin through down-regulating MDR1 expression.
abstract: Cisplatin (DDP) has been successfully used in the treatment of gastric cancer; however, resistance of gastric tumors to cisplatin has also resulted in frequent treatment failure. To investigate the effect of sorafenib in reversing the resistance of human gastric cancer cell line SGC7901/DDP to treatment by cisplatin, and to examine possible underlying mechanisms. A SGC7901/DDP cell line was treated with different concentrations of sorafenib, with and without cisplatin. The reversing ability of sorafenib on cisplatin treatment was examined using MTT, FACS, and xenograft models. Western blotting and immunofluorescence were used to determine expressions of MDR1, p-Akt, and p-ERK. Sorafenib inhibited proliferation of human gastric cancer cell line SGC7901/DDP, both when used alone and in combination with cisplatin. Expression levels of MDR1, p-Akt, and p-ERK were significantly decreased after sorafenib treatment. Sorafenib may reverse resistance of human gastric cancer cell line SGC7901/DDP to cisplatin through down-regulating MDR1 expression.
authors.affiliation: Division 1 of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Huang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xue
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D000077157:Sorafenib; D013274:Stomach Neoplasms / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D002945:Cisplatin