Song Wei, Jiang Rui, Zhao Chun-Ming
Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
Asian Pac J Cancer Prev. 2012;13(11):5619-25. doi: 10.7314/apjcp.2012.13.11.5619.
Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi- drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance- associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -π (GST-π) and RhoE, and transcriptional activation of AP-1 and NF-κB in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.
胃癌是全球癌症死亡的主要原因之一,多药耐药性(MDR)是胃癌化疗失败的一个重要因素。最近的研究表明,整合素连接激酶(ILK)参与人类肿瘤的转移,ILK表达沉默可抑制几种培养的人类癌细胞的转移。然而,ILK在逆转人类胃癌多药耐药性中的作用和潜在机制尚不完全清楚。在本报告中,我们重点研究了ILK表达沉默在人类胃癌SGC7901/DDP细胞多药耐药逆转中的作用,包括对顺铂的药物敏感性增加、细胞凋亡率、罗丹明-123在细胞内的积累,以及多药耐药基因(MDR1)、多药耐药相关蛋白(MRP1)、切除修复交叉互补基因1(ERCC1)、谷胱甘肽S-转移酶-π(GST-π)和RhoE的mRNA和蛋白表达降低,以及ILK沉默的SGC7901/DDP细胞中AP-1和NF-κB的转录激活。我们还发现p-Akt和p-ERK的水平降低。结果表明,ILK可能通过阻断人类胃癌中的PI3K-Akt和MAPK-ERK途径,作为对抗多药耐药性的潜在治疗策略。