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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

Knockdown of PRKD2 Enhances Chemotherapy Sensitivity in Cervical Cancer via the TP53/CDKN1A Pathway

Author(s): Ruijing Feng, Xin Wang, Hongwei Chen, Chen Cao, Ting Liu, Tong Zhao, Huang Chen, Rui Tian, Yangyang Ni, Xun Tian, Zheng Hu*, Ji Ma* and Danni Gong*

Volume 23, Issue 2, 2023

Published on: 06 October, 2022

Page: [159 - 170] Pages: 12

DOI: 10.2174/1568009622666220822191039

Price: $65

Abstract

Background: Chemotherapy is the common treatment for cervical cancer, and the occurrence of drug resistance seriously affects the therapeutic effect of cervical cancer. Our previous study found that PRKD2 mutations occurred only in cervical cancer patients with chemotherapy resistance. However, the relationship between PRKD2 and drug resistance of cervical cancer remains unknown.

Objective: We aim to clarify the relationship between PRKD2 and drug resistance of cervical cancer.

Methods: Samples of patient tumor tissue were collected before chemotherapy and sequenced by WES. Chemotherapy clinical response was determined by measuring tumor volume. The expression of PRKD2, cell viability, and apoptosis were assessed by qRT-PCR, Western blot, CCK8, and flow cytometry in SiHa and ME180 cells after transfected with siPRKD2. The chemotherapy sensitivity signaling- related proteins were analyzed by Western blot. The expression levels of PRKD2, TP53, and CDKN1A in tissues were detected by immunohistochemistry staining.

Results: The expression of PRKD2 was higher in chemotherapy-resistant cervical cancer patients. PRKD2 knockdown increased the chemotherapy sensitivity of cervical cancer cells via the TP53/CDKN1A pathway, which led to G1 arrest and cell apoptosis. Furthermore, downregulation of PRKD2 enhances chemotherapeutic sensitivity in cervical cancer patients through the TP53/CDKN1A pathway.

Conclusion: In summary, PRKD2 may be a promising therapeutic target to improve the efficacy of chemotherapy.

Keywords: Cervical cancer, chemotherapy sensitivity, PRKD2, TP53/CDKN1A pathway, whole exome sequencing, drug resistance.

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