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Protective effects of lidocaine on polycystic ovary syndrome through modulating ovarian granulosa cell physiology via PI3K/AKT/mTOR pathway

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Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine condition in women that causes adverse reproductive and metabolic effects. PCOS is a heterogeneous disorder and its pathogenesis is affected by different factors. Thus, the criteria for diagnosing PCOS, disease and availability of treatment options vary widely across different countries. Lidocaine has been proven to inhibit the proliferation of a variety of cancer cell types, and can be used alone or in combination with other drugs for the treatment of numerous types of disease. The present study aimed to determine whether lidocaine was able to reduce human ovarian granulosa cell tumor cell line KGN cell proliferation and provide a novel insight into potential therapeutic strategies for PCOS. KGN cells were treated alone with lidocaine at different concentrations, or with lidocaine and insulin-like growth factor-1 (IGF-1; a phosphoinositide 3-kinase (PI3K)/Protein kinase B (AKT) signaling pathway agonist) in combination for 48 h. The proliferative ability of KGN cells was detected using an 3-(45)-dimethylthiahiazo (-z-y1)-35-di- phenytetrazoliumromide (MTT) assay, and cell apoptosis was detected using flow cytometry. The expression levels of proteins and mRNAs were measured using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. The results of the present study revealed that lidocaine significantly suppressed KGN cell proliferation and increased apoptosis. Lidocaine significantly downregulated the protein expression levels of phosphorylated (p)-AKT and p-mTOR, but had no effect on their transcriptional levels. Treatment with IGF-1, could reverse the lidocaine-induced abnormal expression of PI3K/AKT signaling pathway-related proteins. Moreover, treatment with IGF-1 could reverse all the effects of lidocaine on KGN cells. In conclusion, the findings of the present study indicated that lidocaine may inhibit KGN cell proliferation and induce apoptosis by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. These results revealed the potential inhibitory effect of lidocaine on the proliferation of KGN cells and its underlying mechanism of action, providing a novel insight into potential therapeutic strategies for PCOS.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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  1. Haixia Xiong and Qiong Hu have equal contributors.

Authors and Affiliations

  1. Department of Anesthesiology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430015, China

    Haixia Xiong

  2. Department of Obstetrics and Gynecology, Central Theater General Hospital of PLA, Wuhan, 430000, China

    Qiong Hu

  3. Department of Pain, Affiliated Hospital of Jianghan University, 168 Hongkong Road, Jiang’an, Wuhan, Hubei, 430015, People’s Republic of China

    Qun Jiang

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  1. Haixia Xiong
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  2. Qiong Hu
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  3. Qun Jiang
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HX and QH contributed to the study design, data collection, statistical analysis, data interpretation and manuscript preparation. QJ contributed to data collection, statistical analysis and manuscript preparation. HX and QH confirm the authenticity of all the raw data. All authors read and approved the final manuscript.

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Correspondence to Qun Jiang.

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Xiong, H., Hu, Q. & Jiang, Q. Protective effects of lidocaine on polycystic ovary syndrome through modulating ovarian granulosa cell physiology via PI3K/AKT/mTOR pathway. Cytotechnology 74, 283–292 (2022). https://doi.org/10.1007/s10616-022-00528-0

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