1. Academic Validation
  2. ClC-3 inhibition induces autophagy to reverse cisplatin resistance in cervical cancer via the Akt/mTOR pathway

ClC-3 inhibition induces autophagy to reverse cisplatin resistance in cervical cancer via the Akt/mTOR pathway

  • Biochim Biophys Acta Mol Basis Dis. 2025 Sep 2;1872(1):168030. doi: 10.1016/j.bbadis.2025.168030.
Jiayi Shen 1 Duoyi Zhang 2 Qi Zheng 1 Zhiyun Zhang 1 Tianhong Zhu 2 Yongming Du 2 Fubin Zhang 3 Yutao Guan 4
Affiliations

Affiliations

  • 1 Health Science Center, Ningbo University, Ningbo 315211, China.
  • 2 Gynecology and Obstetrics, The First Affiliated Hospital of Ningbo University, Ningbo 315000, China.
  • 3 Gynecology and Obstetrics, The First Affiliated Hospital of Ningbo University, Ningbo 315000, China. Electronic address: 124343547@qq.com.
  • 4 Gynecology and Obstetrics, The First Affiliated Hospital of Ningbo University, Ningbo 315000, China. Electronic address: 2309732100@qq.com.
Abstract

Cervical Cancer is one of the most prevalent types of Cancer among women. Nowadays, surgery is still the primary treatment for cervical Cancer. Cisplatin was regarded as the standard medication for non-surgical therapy. Unfortunately, some patients respond poorly to cisplatin, resulting in a significantly reduced survival rate. Our earlier study revealed that chloride channel-3 (ClC-3) is highly expressed in cervical Cancer and Other researchers revealed a tight relationship between ClC-3 and autophagy-induced chemoresistance in different tumor types. Consequently, the purpose of this article is to figure out the link between ClC-3-related Autophagy and cisplatin sensitivity in cervical Cancer. We discovered that inhibiting ClC-3 expression could enhance the sensitivity of cervical Cancer cell line (SiHa) to cisplatin and even reverse the cisplatin resistance in a cisplatin-resistant cervical Cancer cell line (SiHa/DDP). This process was initiated by the cell Autophagy which the Akt-mTOR pathway mediated. A ClC-3 specific inhibitor (Chlorotoxin TFA, CLTX) made cervical Cancer xenograft implantation more sensitive to cisplatin in vivo. All these findings revealed the mechanism and connection between ClC-3 and cisplatin sensitivity in cervical Cancer, as well as provided new light into the application of the ClC-3 specific inhibitor for cisplatin sensitization in cervical Cancer.

Keywords

Autophagy; Cervical cancer; Chloride channel-3; Cisplatin resistance.

Figures
Products