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Fig. 8 | Stem Cell Research & Therapy

Fig. 8

From: Human menstrual blood-derived stem cells reverse sorafenib resistance in hepatocellular carcinoma cells through the hyperactivation of mitophagy

Fig. 8

Red: sorafenib-related events. Blue: MenSC-related events. For adaptation to long-term sorafenib treatment, autophagy was activated in HCC-SR cells and maintained a balanced state by removing damaged mitochondria and other autophagic substrates. This kind of autophagy plays a protective role in the tumour progression of HCC-SR cells and helps to maintain sorafenib resistance. In addition, during HCC cell resistance to sorafenib, BNIP3 and BNIP3L were silenced by DNA methylation (left). MenSCs upregulated BNIP3 and BNIP3L expression via TET2-mediated active demethylation. BNIP3 and BNIP3L are involved in promoting autophagic initiation and mitochondrial membrane potential reduction-related mitochondrial dysfunction and directly interact with LC3 to target mitochondria for removal by autophagosomes. When BNIP3 and BNIP3L levels were abundantly restored, the above-mentioned functions of BNIP3 and BNIP3L were also enlarged and induced hyperactivation of mitophagy. Hyperactivation of mitophagy disrupted the balance of protective autophagy in HCC-SR cells, which eventually led HCC-SR cells to undergo autophagic cell death (right). The figure was created with BioRender.com

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Stem Cell Research & Therapy

ISSN: 1757-6512