CXCR4 blockade sensitizes osteosarcoma to doxorubicin by inducing autophagic cell death via PI3K‑Akt‑mTOR pathway inhibition

• DOI: 10.3892/ijo.2021.5229
• Publication Date: 2021-05-31T13:47:00Z
• Authors: Yu-Xin Liao; Ji-Yang Lv; Zi-Fei Zhou; Tian-Yang Xu; Dong Yang; Qiu-Ming Gao; Lin Fan; Guo-Dong Li; Hai-Yang Yu; Kai-Yuan Liu
• Keywords: RPTOR

Doxorubicin is one of the most frequently used chemotherapy drugs in treatment osteosarcoma (OS), but emergence chemoresistance often leads to failure. C‑X‑C motif chemokine receptor 4 (CXCR4) has been demonstrated regulate OS progression and metastasis. However, whether CXCR4 also involved its molecular mechanisms yet be fully elucidated. In present study, CXCR4‑mediated autophagy for was investigated by western blot analysis, transmission electron microscopy confocal microscopy. silencing enhanced doxorubicin‑induced apoptosis reducing P‑glycoprotein CXCR4+ LM8 cells, while overexpression promoted doxorubicin resistance CXCR4‑ Dunn cells. Furthermore, with or without increased expression beclin 1 light chain 3B, number autophagosomes autolysosomes, as well induced autophagic flux activation suppressing PI3K/AKT/mTOR signaling pathway. addition, pretreatment inhibitor bafilomycin A1 attenuated abrogation‑induced cell death. Finally, antagonist AMD3100 synergistically reinforced antitumor effect an orthotopic mouse model. Taken together, study revealed that inhibition sensitizes inducing Therefore, targeting CXCR4/autophagy axis may a promising therapeutic strategy overcome resistance.