Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors

Hyeon-Ok Jin; Sung-Eun Hong; Jin-Ah Park; Yoon Hwan Chang; Young Jun Hong; In-Chul Park; Jin Kyung Lee

doi:10.1038/srep28945

journal article Open Access Jun 30, 2016

Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors

Hyeon-Ok Jin

Sung-Eun Hong Jin-Ah Park

Yoon Hwan Chang Young Jun Hong In-Chul Park Jin Kyung Lee

Scientific Reports Vol. 6 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep28945

Abstract

AbstractAs the activation of autophagy contributes to the efficacy of many anticancer therapies, deciphering the precise role of autophagy in cancer therapy is critical. Here, we report that the dual mTORC1/2 inhibitors PP242 and OSI-027 decreased cell viability but did not induce apoptosis in the non-small cell lung cancer (NSCLC) cell lines H460 and A549. PP242 induced autophagy in NSCLC cells as demonstrated by the formation of massive vacuoles and acidic vesicular organelles and the accumulation of LC3-II. JNK was activated by PP242, and PP242-induced autophagy was blocked by inhibiting JNK pathway with SP600125 or JNK siRNA, suggesting that JNK activation is required for the mTORC1/2 inhibitor-mediated induction of autophagy in NSCLC cells. Inhibiting JNK or autophagy increased the sensitivity of H460 cells to mTORC1/2 inhibitors, indicating that JNK or autophagy promoted survival in NSCLC cells treated with mTORC1/2 inhibitors. Together, these data suggest that combining mTORC1/2 inhibitors with inhibitors of JNK or autophagy might be an effective approach for improving therapeutic outcomes in NSCLC.

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Published: Jun 30, 2016
Vol/Issue: 6(1)
License: View

Authors

Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA 1 Department of Environmental Health ,

Cite This Article

Hyeon-Ok Jin, Sung-Eun Hong, Jin-Ah Park, et al. (2016). Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors. Scientific Reports, 6(1). https://doi.org/10.1038/srep28945

Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors

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