HMGB1‑mediated autophagy confers resistance to gemcitabine in hormone‑independent prostate cancer cells

Zhang,Yi‑Xiang; Yuan,Ye‑Qing; Zhang,Xue‑Qi; Huang,Dong‑Long; Wei,Yu‑Ying; Yang,Jiang‑Gen

doi:10.3892/ol.2017.6965

HMGB1‑mediated autophagy confers resistance to gemcitabine in hormone‑independent prostate cancer cells

Authors:
- Yi‑Xiang Zhang
- Ye‑Qing Yuan
- Xue‑Qi Zhang
- Dong‑Long Huang
- Yu‑Ying Wei
- Jiang‑Gen Yang
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Affiliations: Department of Urology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
Published online on: September 15, 2017 https://doi.org/10.3892/ol.2017.6965
Pages: 6285-6290

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Abstract

As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone‑independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines. The results demonstrated that the autophagy markers were induced significantly in HIPC cells subsequent to gemcitabine treatment. Meanwhile, administration of gemcitabine to HIPC cells increased the expression of high mobility group box1 (HMGB1). Furthermore, the gemcitabine‑induced autophagy response was attenuated in stable HIPC cells harboring HMGB1 shRNA. Notably, the HIPC cells stably transfected with HMGB1 shRNA or treated with autophagy inhibitors were more sensitive to gemcitabine compared with the control group. These data suggested that inhibition of HMGB1 increased the sensitivity to gemcitabine by decreasing autophagy response in HIPC cells. Overall, the present findings demonstrate a new mechanism for the resistance to gemcitabine in HIPC cell lines.

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