The Korean Journal of Physiology and Pharmacology

  • 제27권1호
  • /
  • Pages.21-29
  • /
  • 2023
  • /
  • 1226-4512(pISSN)
  • /
  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways

  • Gang Wang (Department of Gynecology, Wuhan Third Hospital-Tongren Hospital of Wuhan University) ;
  • Baisha Ouyang (Department of Obstetrics and Gynaecology, Taikang Tongji (Wuhan) Hospital) ;
  • Fang Jing (Department of Gynecology, Wuhan Third Hospital-Tongren Hospital of Wuhan University) ;
  • Xiaoyan Dai (Department of Gynecology, Wuhan Third Hospital-Tongren Hospital of Wuhan University)
  • 투고 : 2022.03.14
  • 심사 : 2022.09.13
  • 발행 : 2023.01.01
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초록

The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof-function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin's efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin's efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.

키워드

과제정보

This work was supported by a research grant provided by Wuhan Municipal Health and Family Planning Commission (Grant No. WX18D22).

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