目的：探讨RNAi沉默酪氨酸激酶受体RON（recepteur d’origine nantais）基因对人结肠癌HT-29细胞侵袭和对抗肿瘤药物敏感性的影响。 方法： 构建RON基因的RNAi慢病毒载体Lv-RON-siRNA。Real-time PCR和Western blotting检测RON基因的沉默效率及RON蛋白表达水平；Transwell侵袭实验和ATP-TCA（ATP-tumor chemosensitivity assay）检测RON基因对HT-29细胞侵袭和对药物敏感性的影响。 结果： 慢病毒载体Lv-RON-siRNA感染HT-29细胞对RON基因的沉默效果达到70%。Lv-RON-siRNA感染后，HT-29细胞侵袭力较对照组明显降低（ 0.97±0.072 vs 1.29±0.076，P<0.05）。Lv-RON-siRNA感染后，HT-29细胞对5-氟尿嘧啶(5-fluorouraci, 5-FU)的IC90值和IC50值分别为(14.28±1.34)、(8.93±1.20) μg/ml，顺铂（cisplatin, DDP)的IC90值和IC50值分别为(1.91±0.22)、(0.64±0.07) μg/ml，均明显低于对照组（P<0.01）。 结论： 沉默RON基因表达能抑制HT-29细胞的侵袭力，提高细胞对5-FU和DDP的敏感性

Objective : To investigate the effect of receptor tyrosine kinase recepteur d’origine nantais (RON) gene silencing on the invasion and anticancer drug resistance of human colon carcinoma HT-29 cells. Methods: RNAi lentiviral vector targeting RON gene (Lv-RON-siRNA) was constructed. The efficiency of Lv-RON-siRNA on RON gene silence and RON protein level in HT-29 cells were detected by real-time PCR and Western blotting, respectively. The effects of Lv-RON-siRNA on invasion and drug resistance of HT-29 cells were observed by Transwell assay and ATP-TCA (ATP-tumor chemosensitivity assay). Results: The silencing effect of Lv-RON-siRNA on RON gene expression in HT-29 cells reached 70%. Compared with the control group, the invasion of HT-29 cells in Lv-RON-siRNA infection group was decreased（097±0.07 vs 1.29±0.08, P<0.05). The values of IC90 and IC50 of HT-29 cells infected with Lv-RON-siRNA to 5-FU were (14.28±1.34) μg/ml and (8.93±1.2) μg/ml, respectively. The IC90 and IC50 of HT-29 cells infected with Lv-RON-siRNA to cisplatin (DDP) were (1.91±0.22) μg/ml and (0.64±0.07) μg/ml, respectively, and were significantly lower than those in the control group (P<0.01). Conclusion: Silencing RON gene expression can decrease the invasion ability of HT-29 cells and increase the sensitivity of HT-29 cells to 5-FU and DDP.

宁波市自然科学基金资助项目（No.2008A610082）