Fig. 7

Inhibition effects of combination therapy with Lenvatinib and hydroxychloroquine were much better than Lenvatinib alone. a–e HCCLM3 orthotopically bearing mice were treated with HCQ, lenvatinib (5 mg/kg or 10 mg/kg) alone or combination with lenvatinib 5 mg/kg and HCQ 50 mg/kg, normal saline as control. a Representative images of the HCCLM3 orthotopic HCC tumors from each group (n = 5 mice/group). b Tumor weight in both low and high lenvatinib treatment groups was much lower than that in control group, while there was no difference between control and HCQ groups. The best inhibition efficacy was found in combination therapy group. c Representative H&E staining images of lung tissues of different treatment groups. Blue arrows indicated lung metastasis. Scale bar, 100 μm. d The mean number of lung metastasis in mice of each group. e The results of Kaplan–Meier survival curves for tumor bearing mice indicated that combination treatment prolonged OS of xenograft mice models bearing HCCLM3 significantly (P < 0.001), even much better than high dose of lenvatinib treatment group (P = 0.006). The P values for each comparison are as followed: Control versus HCQ (P = 0.065), Control versus LV5 (P = 0.023), Control versus LV10 (P < 0.001). f Schematic depiction of the underlying mechanisms of STOML2 upregulation in HCC and its functional role of facilitating HCC proliferation, metastasis and drug insensitivity via promoting PINK1-Parkin-mediated mitophagy. *P < 0.05; **P < 0.01; ***P < 0.001; ns no significance, LV5 lenvatinib 5 mg/kg, LV10 lenvatinib 10 mg/kg