PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway

Cancer Biol Ther. 2018 Mar 4;19(3):222-229. doi: 10.1080/15384047.2017.1416936. Epub 2018 Jan 25.

Abstract

Phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) is overexpressed in different types of human cancer. We previously reported the important role of PIK3R3 in colorectal cancer (CRC). However, the prognosis effect of PIK3R3 in CRC is still remaining unclear. In this study, we explored online clinical databases to analyze the prognosis differences between higher and lower expression of PIK3R3 in CRC patients. Interestingly, we found that better disease-free survival (DFS) were occurred in patients with higher expression of PIK3R3, but there is no significant difference in overall survival (OS). For further, we showed that PIK3R3 could enhance 5-FU induced apoptosis by regulating the expression of thymmidine phosphorylase (TP). In conclusion, PIK3R3 could be considered as a predictor of 5-FU sensitivity for personalized treatment, and a therapeutic target for colorectal cancer.

Keywords: 5-fluorouracil; Colon cancer; Disease free survival; Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3); overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Apoptosis / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Datasets as Topic
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • HT29 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Thymidine Phosphorylase / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • NF-kappa B
  • Thymidine Phosphorylase
  • Phosphatidylinositol 3-Kinases
  • PIK3R3 protein, human
  • Fluorouracil

Grants and funding

National Natural Science Foundation of China (NSFC), 81372662 National Natural Science Foundation of China (NSFC), 81372323.