title: PIK3CA and PIK3CB silencing by RNAi reverse MDR and inhibit tumorigenic properties in human colorectal carcinoma.
abstract: 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.
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Wu
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wen
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Gao
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: He
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China.
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Department of Pathology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong Province, China. dongtianbz@163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Tian
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D034622:RNA Interference / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C497132:PIK3CB protein, human
keywords: Colorectal cancer; Gene therapy; MDR; PIK3CA; PIK3CB; Stably transfected cell lines