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STAT3 inhibitor BBI608 reduces patient-specific primary cell viability of cervical and endometrial cancer at a clinical-relevant concentration

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Abstract

Purpose

Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro.

Methods

PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3).

Results

The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer.

Conclusions

In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials.

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Acknowledgements

This work was supported by the Guangdong Basic and Applied Basic Research Foundation [2019A1515011725, 2019A1515011191]; Science and technology projects of GDPH [2018bq03]; NSFC Incubation Program of GDPH [KY012021158]; Guangdong Medical Science and Technology Research Fund [A2020016, A2020537].

Author information

Author notes

  1. Jing Chen, Shuting Huang and Huawen Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China

    Jing Chen, Shuting Huang, Haishan Zeng, Jiemei Hu, Huihua Cai & Mubiao Liu

  2. Department of Gynecology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, Guangdong, People’s Republic of China

    Huawen Li, Pengfei Deng, Ting Song & Mubiao Liu

  3. Guangdong Procapzoom Biosciences, Inc, Guangzhou, Guangdong, China

    Yun Li, Yanchun Lin, Tian Guan & Haoyu Zeng

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  1. Jing Chen
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Contributions

M-BL, and H-YZ designed research; JC, S-TH, and W-HL performed research and analyzed data; H-SZ, J-MH, Y-CL, H-HC, and P-FD collected tumor samples; and S-TH, TS, TG composed the paper.

Corresponding author

Correspondence to Mubiao Liu.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All of the protocols using human specimens were approved by the Zhuhai People’s Hospital, and informed consent was obtained from all of the subjects.

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Chen, J., Huang, S., Li, H. et al. STAT3 inhibitor BBI608 reduces patient-specific primary cell viability of cervical and endometrial cancer at a clinical-relevant concentration. Clin Transl Oncol 25, 662–672 (2023). https://doi.org/10.1007/s12094-022-02970-0

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