The Journal of Practical Medicine >

2025 , Vol. 41 >Issue 4: 490 - 499

DOI: https://doi.org/10.3969/j.issn.1006-5725.2025.04.005

Basic Research

CCCTC⁃binding factors promote the formation of oxaliplatin related gastric cancer drug-tolerant cells by resisting apoptosis

  • Zonglin LI ,
  • Chunlin FENG ,
  • Xin LIU ,
  • Xingming SHU ,
  • Min. SONG
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  • Department of General Surgery （Gastrointestinal Surgery），the Affiliated Hospital of Southwest Medical University，Luzhou 646000，Sichuan，China

Received date: 2024-10-18

  Online published: 2025-02-28

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Abstract

Objective To investigate the role of CCCTC-binding factor （CTCF） in the development of oxaliplatin （OXA）-induced gastric cancer drug-tolerant cells （DTCs） and to preliminarily elucidate its underlying mechanisms. Methods The DTCs model of gastric cancer was established by treating MGC803 cells with OXA. Overexpression and knockdown of CTCF in MGC803 cells were performed to observe their effects on the formation of DTCs in gastric cancer. Additionally， Bcl2-like protein 1 （BCL2L1） was knocked down in CTCF-overexpressing cells， and its impact on DTCs formation was evaluated. Flow cytometry was used to analyze the effects of varying CTCF/BCL2L1 expression levels on the apoptosis of gastric cancer cells under OXA treatment. Immunohistochemistry （IHC） was employed to detect the expression levels of CTCF/BCL2L1 in gastric cancer tissues， and the therapeutic outcomes of neoadjuvant chemotherapy in patients with different CTCF/BCL2L1 expression levels were assessed. Results Gastric cancer DTCs can be obtained following a regimen of continuous treatment of MGC803 cells with a specific concentration of oxaliplatin （OXA， 1.5 μmol/L） for 5 days， followed by an additional 5-day culture period post-treatment cessation. The upregulation of CTCF has been shown to facilitate the formation of DTCs in gastric cancer， whereas its downregulation inhibits this process （P < 0.05）. In MGC803 gastric cancer cells， the expression level of BCL2L1 is positively correlated with that of CTCF. Knockdown of BCL2L1 in MGC803 cells overexpressing CTCF can reverse the pro-DTC formation effect of CTCF （P < 0.05）. Overexpression of CTCF confers resistance to OXA-induced apoptosis in gastric cancer cells， and this anti-apoptotic effect can be reversed by BCL2L1 knockdown in MGC803 cells overexpressing CTCF （P < 0.05）. In the tumor tissues of the majority of gastric cancer patients， the expression levels of BCL2L1 are positively correlated with those of CTCF， and the efficacy of neoadjuvant chemotherapy is notably reduced in patients with high expression of the CTCF/BCL2L1 axis compared to those with low expression （P < 0.05）. Conclusion CTCF promotes the formation of OXA-related gastric cancer DTCs by upregulating BCL2L1 expression and inhibiting apoptosis， making the CTCF/BCL2L1 axis a potential therapeutic target for DTCs in gastric cancer.

Key words： gastric cancer; oxaliplatin; drug tolerant cells; apoptosis; CTCF; BCL2L1

Cite this article

Zonglin LI , Chunlin FENG , Xin LIU , Xingming SHU , Min. SONG . CCCTC⁃binding factors promote the formation of oxaliplatin related gastric cancer drug-tolerant cells by resisting apoptosis[J]. The Journal of Practical Medicine, 2025 , 41(4) : 490 -499 . DOI: 10.3969/j.issn.1006-5725.2025.04.005

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