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Int J Mol Med. 2019 Aug;44(2):523-534. doi: 10.3892/ijmm.2019.4231. Epub 2019 Jun 6.

T7 peptide cytotoxicity in human hepatocellular carcinoma cells is mediated by suppression of autophagy.

Author information

1
Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
2
Department of Hepatobiliary Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.
3
Department of Hepatobiliary Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, Shandong 250117, P.R. China.

Abstract

The T7 peptide, an active fragment of full‑length tumstatin [the non‑collagenous 1 domain of the type IV collagen α3 chain, α3 (IV) NC1], has exhibited potential antitumor effects in several types of cancer cells. However, the mechanism underlying its action against human hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the role of autophagy in T7 peptide‑induced cytotoxicity in HCC cells in vitro and in vivo. The results revealed that the T7 peptide significantly reduced cell viability and induced cell cycle arrest in HCC cells. The T7 peptide induced apoptosis in HCC cells through upregulation of Bax, Fas, and Fas ligand, and through upregulation of the anti‑apoptotic protein Bcl‑2. In addition, treatment with the T7 peptide induced protective autophagy in HCC cells. Blocking autophagy by 3‑methyladenineor bafilomycin A1 enhanced T7 peptide‑induced apoptosis. Furthermore, co‑treatment with MK‑2206 (an Akt specific inhibitor) or rapamycin (an inhibitor of mTOR) enhanced T7 peptide‑induced autophagy, whereas co‑treatment with insulin (an activator of the Akt/mTOR signaling pathway) alleviated T7 peptide‑induced autophagy, which suggested that the T7 peptide may induce autophagy activation via inhibition of the Akt/mTOR signaling pathway. Taken together, the present results demonstrated that suppression of autophagy potentiated the cytotoxic effects of the T7 peptide, and suggested that the T7 peptide may serve as a potential alternative compound for HCC therapy.

PMID:
31173192
DOI:
10.3892/ijmm.2019.4231

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