Suppression of p53 potentiates chemosensitivity in nutrient‑deprived cholangiocarcinoma cells via inhibition of autophagy

Hu,Fei; Guo,Xian‑Ling; Zhang,Shan‑Shan; Zhao,Qiu‑Dong; Li,Rong; Xu,Qing; Wei,Li‑Xin

doi:10.3892/ol.2017.6449

Suppression of p53 potentiates chemosensitivity in nutrient‑deprived cholangiocarcinoma cells via inhibition of autophagy

Authors:
- Fei Hu
- Xian‑Ling Guo
- Shan‑Shan Zhang
- Qiu‑Dong Zhao
- Rong Li
- Qing Xu
- Li‑Xin Wei
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Affiliations: Department of Medical Oncology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China, Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, P.R. China
Published online on: June 21, 2017 https://doi.org/10.3892/ol.2017.6449
Pages: 1959-1966
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor protein p53 has been intensively studied as a major tumor suppressor. The activation of p53 is associated with various anti‑neoplastic functions, including cell senescence, cell cycle arrest, apoptosis and inhibition of angiogenesis. However, the role of p53 in cancer cell chemosensitivity remains unknown. Cholangiocarcinoma cell lines QBC939 and RBE were grown in full‑nutrient and nutrient‑deprived conditions. The cell lines were treated with 5‑fluorouracil or cisplatin and the rate of cell death was determined in these and controls using Cell Counting Kit‑8 and microscopy‑based methods, including in the presence of autophagy inhibitor 3MA, p53 inhibitor PFT‑α or siRNA against p53 or Beclin‑1. The present study demonstrated that the inhibition of p53 enhanced the sensitivity to chemotherapeutic agents in nutrient‑deprived cholangiocarcinoma cells. Nutrient deprivation‑induced autophagy was revealed to be inhibited following inhibition of p53. These data indicate that p53 is important for the activation of autophagy in nutrient‑deprived cholangiocarcinoma cells, and thus contributes to cell survival and chemoresistance.

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