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Stanniocalcin 2 induces oxaliplatin resistance in colorectal cancer cells by upregulating P-glycoprotein

机译:Stanniocalcin 2通过上调P糖蛋白诱导大肠癌细胞对奥沙利铂的耐药性

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Multidrug resistance (MDR) limits the anticancer effects of chemotherapy in patients with metastatic colorectal cancer (CRC). Oxaliplatin is a common component of combinational therapeutic regimens administered to patients with metastatic CRC; however, it is also used as a constituent of adjuvant therapy for patients at a risk of recurrent disease. In the present study, we investigated the role of stanniocalcin 2 (STC2) in chemoresistance. STC2 knockdown sensitized chemoresistant CRC cells to oxaliplatin. Moreover, the expression of exogenous STC2 in chemonaive CRC cells induced oxaliplatin resistance. We confirmed that STC2 upregulated P-glycoprotein (P-gp) expression in CRC cells. Furthermore, shRNA against phosphoinositide 3-kinase (PI3K) or Akt inhibited the action of STC2 on P-gp upregulation and MDR in CRC. To our knowledge, this is the first report to demonstrate the induction of oxaliplatin resistance in CRC cells in response to STC2 stimulation of P-gp via the PI3K/Akt signaling pathway.
机译:多药耐药性(MDR)限制了化疗对转移性结直肠癌(CRC)患者的抗癌作用。奥沙利铂是转移性CRC患者联合治疗方案的常见组成部分。但是,它也可作为有复发疾病风险的患者辅助治疗的组成部分。在本研究中,我们调查了斯坦钙钙蛋白2(STC2)在化学抗性中的作用。 STC2敲低使化学耐药性CRC细胞对奥沙利铂敏感。此外,外源性STC2在化学性CRC细胞中的表达诱导了奥沙利铂抗性。我们证实,STC2上调了CRC细胞中的P-糖蛋白(P-gp)表达。此外,针对磷酸肌醇3-激酶(PI3K)或Akt的shRNA抑制了STC2对CRC中P-gp上调和MDR的作用。据我们所知,这是第一份证明通过PI3K / Akt信号通路响应STC2刺激P-gp而在CRC细胞中诱导奥沙利铂抗性的报告。

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