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.