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SPP1 inhibition improves the cisplatin chemo-sensitivity of cervical cancer cell lines

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Abstract

Purpose

Cisplatin (DDP)-based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. In the present study, we aimed to explore the effects of SPP1 on the proliferation and apoptosis rate of the HeLa cervical cancer cell line with cisplatin (DDP) resistance.

Methods

Microarray analysis was employed to select differentially expressed genes in cervical cancer tissues and adjacent tissues. Then, we established a DDP-resistant HeLa cell line (res-HeLa). Western blotting was used to detect SPP1 expression in both tissue and cells. After the transfection with si-SPP1 and pcDNA3.1-SPP1, colony formation and MTT assays were applied to detect cell proliferation changes. Flow cytometry was employed to detect the cell apoptosis rate. Western blotting was performed to verify the activation of PI3K/Akt signal pathway proteins related to DDP resistance.

Results

SPP1 was overexpressed in cervical cancer tissues and cell lines. Compared to normal HeLa cells, expression of SPP1 was significantly enhanced in res-HeLa cells. SPP1 knockdown resulted in repressed proliferation and enhanced apoptosis of res-HeLa cells, which could be reversed by SPP1 overexpression in HeLa cells. Additionally, downregulation of SPP1 improved the DDP sensitivity of HeLa by inhibiting the PI3K/Akt signaling pathway.

Conclusion

SPP1 inhibition could suppress proliferation, induce apoptosis and increase the DDP chemo-sensitivity of HeLa cells.

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Author notes

  1. Xing Chen and Dongsheng Xiong contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, 317000, Zhejiang, China

    Xing Chen, Liya Ye, Huichun Yang, Shuangshuang Mei, Jinhong Wu & Shanshan Chen

  2. State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China

    Dongsheng Xiong

  3. Department of Obstetrics and Gynecology, General Hospital of Tianjin Medical University, No. 154 Anshan Road, Heping District, Tianjin, 300052, China

    Ruoran Mi

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  1. Xing Chen
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Correspondence to Ruoran Mi.

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The authors declare that there are no competing interests associated with the manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of General Hospital of Tianjin Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Chen, X., Xiong, D., Ye, L. et al. SPP1 inhibition improves the cisplatin chemo-sensitivity of cervical cancer cell lines. Cancer Chemother Pharmacol 83, 603–613 (2019). https://doi.org/10.1007/s00280-018-3759-5

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  • DOI: https://doi.org/10.1007/s00280-018-3759-5

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