通过RNA干扰使PIK3CA和PIK3CB沉默可逆转多药耐药性并抑制人结直肠癌的致瘤特性。
PIK3CA and PIK3CB silencing by RNAi reverse MDR and inhibit tumorigenic properties in human colorectal carcinoma.
作者信息
Wu Shuhua, Wen Feifei, Li Yangyang, Gao Xiangqian, He Shuang, Liu Mengyao, Zhang Xiangzhi, Tian Dong
机构信息
The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
出版信息
Tumour Biol. 2016 Jul;37(7):8799-809. doi: 10.1007/s13277-015-4691-5. Epub 2016 Jan 8.
Colorectal carcinoma (CRC) is the second most common and frequent cause of cancer-related deaths for men and women in the world. PIK3CA and PIK3CB that reverse multidrug resistance (MDR) can serve as predictive and prognostic markers as well as therapeutic targets for CRC treatment. In the present study, we showed that PIK3CA and PIK3CB are upregulated in CRCs and positively correlated with MDR-1, LRP, and GST-π. Long-term monitoring of 316 CRC patients showed that PIK3CA and PIK3CB were associated with poor survival time as shown by Kaplan-Meier analysis. Furthermore, we found that the downregulation of PIK3CA and PIK3CB reversed MDR; inhibited the capability of proliferation, migration, and invasion of CRC cells; and slowed down the CRC tumor growth in nude mice. Consistent with clinical observations, PIK3CA and PIK3CB significantly increase multidrug resistance of CRC cells in vivo. Together, these results suggest that PIK3CA and PIK3CB may be used as potential therapeutic drug targets for colorectal cancer.
结直肠癌（CRC）是全球男性和女性癌症相关死亡的第二大常见且频发原因。具有逆转多药耐药性（MDR）作用的PIK3CA和PIK3CB可作为结直肠癌治疗的预测和预后标志物以及治疗靶点。在本研究中，我们发现PIK3CA和PIK3CB在结直肠癌中上调，且与MDR-1、LRP和GST-π呈正相关。对316例结直肠癌患者的长期监测显示，Kaplan-Meier分析表明PIK3CA和PIK3CB与较差的生存时间相关。此外，我们发现PIK3CA和PIK3CB的下调可逆转多药耐药性；抑制结直肠癌细胞的增殖、迁移和侵袭能力；并减缓裸鼠体内结直肠癌肿瘤的生长。与临床观察结果一致，PIK3CA和PIK3CB在体内显著增加结直肠癌细胞的多药耐药性。总之，这些结果表明PIK3CA和PIK3CB可能用作结直肠癌潜在的治疗药物靶点。
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