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. 2025 Jun;63(3):2263-2275.
doi: 10.1007/s10528-024-10796-4. Epub 2024 May 9.

Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms

Mahya Ahmadpour Youshanlui #  1 , Hadi Nasiri #  1 , Zahra Valedkarimi  1 , Mohammadreza Sadeghi  1 , Morteza Akbari  1 , Kimia Motlagh Asghari  1 , Fereshteh Jamali  1 , Deniz Abdi  1 , Bahareh Mehramouz  2 , Farnaz Rasi Bonab  1 , Behzad Baradaran  3   4
Affiliations

Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms

Mahya Ahmadpour Youshanlui et al. Biochem Genet. 2025 Jun.

Abstract

After chemotherapy, tumor cells tend to become more aggressive, making it challenging for natural and adaptive immune responses to fight them. This often results in recurrence and metastasis, leading to higher mortality rates. The purpose of this study is to discover the mechanisms that cause chemotherapy resistance, including altered expression of immune checkpoints, in a colorectal cancer cell line. We used conventional methods to culture the SW-1116 colorectal cancer cell line in this study. The MTT assay was used to determine the IC50 and efficacy of Docetaxel and Doxorubicin. After treatment, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze PD-L1, CTLA-4, and VISTA gene expression in the SW-1116 cell line. The upregulation of VISTA expression showed a significant increase (p < 0.0001) in response to both chemotherapy agents. Moreover, the expression of CTLA-4 exhibited a remarkable level of significance (p < 0.0001), and PD-L1 expression also displayed notable significance (p < 0.0001). Chemotherapeutic agents heighten immune checkpoint gene expression, highlighting potential immune response pathway modulation.

Keywords: CTLA-4; Chemotherapy resistency; Colorectal cancer; Immunecheckpoint; PD-L1; VISTA.

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Conflict of interest statement

Declarations. Competing Interests: The authors have not disclosed any competing interests. Ethical Approval: The investigation was approved by Tabriz University of Medical Science’s medical ethics committee, and the ethics Identification Number is IR.TBZMED.VCR.REC.1402.077. This research was carried out by the principles of the Helsinki Declaration. Consent for Publication: Not applicable.

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