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Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands

Identifieur interne : 001206 ( Main/Exploration ); précédent : 001205; suivant : 001207

Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands

Auteurs : Ben Ma [République populaire de Chine] ; Li-Zhong Liang [République populaire de Chine] ; Gui-Qing Liao [République populaire de Chine] ; Yu-Jie Liang [République populaire de Chine] ; Hai-Chao Liu [République populaire de Chine] ; Guang-Sen Zheng [République populaire de Chine] ; Yu-Xiong Su [République populaire de Chine]

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RBID : ISTEX:4756295F731DDF4907B5182AFB4A9B1F9B61E844

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Abstract

Background: The relationship between autophagy and chemotherapy in cancer has been studied a lot recent years. However, there is currently no study on the role of autophagy in chemotherapy of adenoid cystic carcinoma (ACC) of human salivary glands. We hypothesized that autophagy plays a protective role for human salivary gland ACC cells during chemotherapy, diminishes the effect of treatment, and ultimately results in poor sensitivity to chemotherapy. Materials and Methods: After inhibition of autophagy by 5 mM 3‐methyladenine (3MA), 20 μM Chloroquine (CQ), or Beclin‐1 shRNA, we examined the sensitivity of human salivary gland ACC cells to different concentrations of cis‐diamminedichloroplatinum (CDDP) using MTT assay. Also, levels of autophagy in ACC cells treated by CDDP were assessed by western blot, GFP‐LC3 fluorescence and transmission electron microscopy (TEM). Results: Inhibition of autophagy induced by 3MA, CQ, or Beclin‐1 shRNA could all enhance human salivary gland ACC cell death treated by CDDP. And, levels of autophagy in these cells showed a significant increase after treated by CDDP. Conclusion: Autophagy played a protective role for human salivary gland ACC cells during CDDP chemotherapy. Inhibition of autophagy in these cells could enhance cisplatin cytotoxicity‐effects. These findings indicate a novel and promising way to reduce chemotherapy resistance and improve treatment outcome in human salivary gland ACC.

Url:
DOI: 10.1111/jop.12066


Affiliations:


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<div type="abstract" xml:lang="en">Background: The relationship between autophagy and chemotherapy in cancer has been studied a lot recent years. However, there is currently no study on the role of autophagy in chemotherapy of adenoid cystic carcinoma (ACC) of human salivary glands. We hypothesized that autophagy plays a protective role for human salivary gland ACC cells during chemotherapy, diminishes the effect of treatment, and ultimately results in poor sensitivity to chemotherapy. Materials and Methods: After inhibition of autophagy by 5 mM 3‐methyladenine (3MA), 20 μM Chloroquine (CQ), or Beclin‐1 shRNA, we examined the sensitivity of human salivary gland ACC cells to different concentrations of cis‐diamminedichloroplatinum (CDDP) using MTT assay. Also, levels of autophagy in ACC cells treated by CDDP were assessed by western blot, GFP‐LC3 fluorescence and transmission electron microscopy (TEM). Results: Inhibition of autophagy induced by 3MA, CQ, or Beclin‐1 shRNA could all enhance human salivary gland ACC cell death treated by CDDP. And, levels of autophagy in these cells showed a significant increase after treated by CDDP. Conclusion: Autophagy played a protective role for human salivary gland ACC cells during CDDP chemotherapy. Inhibition of autophagy in these cells could enhance cisplatin cytotoxicity‐effects. These findings indicate a novel and promising way to reduce chemotherapy resistance and improve treatment outcome in human salivary gland ACC.</div>
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