2. Academic Validation
  3. ANXA2 and Rac1 negatively regulates autophagy and osteogenic differentiation in osteosarcoma cells to confer CDDP resistance

ANXA2 and Rac1 negatively regulates autophagy and osteogenic differentiation in osteosarcoma cells to confer CDDP resistance

  • Biochem Biophys Res Commun. 2023 Oct 8:676:198-206. doi: 10.1016/j.bbrc.2023.07.006.
Baolong Pan 1,  Yanyu Pan 2,  Shuangneng Wang 1,  Yingying Bai 1,  Xuemei Hu 1,  Yang Yang 1,  Ling Wu 3,  Jianping Liu 4
Affiliations

Affiliations

  • 1 Health Examination Center, Sixth Affiliated Hospital of Kunming Medical University, Yuxi, 653100, Yunnan, China.
  • 2 College of Basic Medical Sciences, Naval Medical University, Shanghai, 200433, China.
  • 3 Department of Blood Composition Production, Central Blood Station of Yuxi City, Yuxi, 653100, Yunnan, China. Electronic address: [email protected].
  • 4 Research Management Department, Sixth Affiliated Hospital of Kunming Medical University, Yuxi, 653100, Yunnan, China. Electronic address: [email protected].
PMID: 37536195 DOI: 10.1016/j.bbrc.2023.07.006
Abstract

Background: Cisplatin (CDDP) is a mainstay chemotherapeutic agent for OS treatment, but drug resistance has become a hurdle to limit its clinical effect. Autophagy plays an important role in CDDP resistance in OS, and in the present study we explored the role of AnxA2 and Rac1 in dictating CDDP sensitivity in OS cells.

Methods: AnxA2 and Rac1 expression levels were examined by Western blot and Autophagy induction was detected by transmission electron miscroscope (TEM) in the clinical samples and OS cell lines. CDDP resistant cells were established by exposing OS cells to increasing doses of CDDP. The effects of AnxA2 and Rac1 knockdown on CDDP sensitivity were evaluated in the cell and animal models.

Results: Reduced Autophagy was associated with the increased expression of AnxA2 and Rac1 in CDDP resistant OS tumor samples and cells. Autophagy suppression promoted CDDP resistance and inducing Autophagy re-sensitized the resistant cells to CDDP treatment in vitro and in vivo. Further, knocking down AnxA2 or Rac1 re-activated Autophagy and attenuated CDDP resistance in OS cells. We further demonstrated that CDDP resistant OS cells displayed a poorer osteogenic differentiation state when compared to the parental cell lines, which was significantly reversed by Autophagy re-activation and AnxA2 or Rac1 silencing.

Conclusion: Our findings revealed a complicated interplay of AnxA2/Rac1, Autophagy induction, and osteogenic differentiation in dictating CDDP resistance in OS cells, suggesting AnxA2 and Rac1 as promising targets to modulate Autophagy and overcome CDDP resistance in OS cells.

Keywords

ANXA2 and Rac1; Autophgy; Cisplatin (CDDP); Drug resistance; Osteogenic differentiation; Osteosarcoma (OS).

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