Probing the Effects of Retinoblastoma Binding Protein 6 (RBBP6) Knockdown on the Sensitivity of Cisplatin in Cervical Cancer Cells

Sep 21, 2026

Cervical cancer remains a major cause of mortality despite advances in therapy, and cisplatin resistance commonly emerges from tumor heterogeneity. This study investigates how retinoblastoma binding protein 6 (RBBP6) expression relates to cisplatin sensitivity in cervical cancer cells. Bioinformatics and the GDSC dataset support an association between the RBBP6/p53/BCL-2 axis and cervical cancer, and multiple CC lines show cisplatin sensitivity. HeLa and Vero cells were treated with siRBBP6 using RNAi, and wild-type p53 and Bcl-2 were quantified by qPCR. Cotreatment analyses used flow cytometry for apoptosis and xCELLigence for real-time growth monitoring. RBBP6 knockdown reduced apoptosis and delayed cisplatin-driven growth inhibition, while p53 stayed unchanged and Bcl-2 was fully repressed, indicating Bcl-2 downregulation as a key mechanism. The non-cancerous Vero control remained viable under combined treatment. These results suggest RBBP6 promotes cisplatin responsiveness and may guide personalized administration based on RBBP6 expression profiles.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

1. Introduction

cells Article Probing the Effects of Retinoblastoma Binding Protein 6 (RBBP6) Knockdown on the Sensitivity of Cisplatin in Cervical Cancer Cells Harshini Mehta 1,†, Melvin Anyasi Ambele 2,3, Ntlotlang Mokgautsi 1 and Pontsho Moela 1, *,† Citation: Mehta, H.; Ambele, M.A.; Mokgautsi, N.; Moela, P. Probing the Effects of Retinoblastoma Binding Protein 6 (RBBP6) Knockdown on the Sensitivity of Cisplatin in Cervical Cancer Cells. Cells 2024, 13, 700 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13080700 Academic Editor: Alexander E. Kalyuzhny Received: 3 January 2024 Revised: 5 April 2024 Accepted: 13 April 2024 Published: 18 April 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Division of Genetics, Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0002, South Africa; [u16025483@tuks.co.za](u16025483@tuks.co.za) (H.M.); [u23040743@tuks.co.za](u23040743@tuks.co.za) (N.M.) 2 Institute for Cellular and Molecular Medicine, Department of Immunology and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa; [melvin.ambele@up.ac.za](melvin.ambele@up.ac.za) 3 Department of Oral and Maxillofacial Pathology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa * [Correspondence: pontsho.moela@up.ac.za](Correspondence: pontsho.moela@up.ac.za) † These authors contributed equally to this work and share first authorship. Abstract: Cervical cancer is a major cause of death in women despite the advancement of current treatment modalities. The conventional therapeutic agent, cisplatin (CCDP), is the standard treatment for CC; however, resistance often develops due to the cancer’s heterogeneity. Therefore, a detailed elucidation of the specific molecular mechanisms driving CC is crucial for the development of targeted therapeutic strategies. Retinoblastoma binding protein 6 (RBBP6) is a potential biomarker associated with cell proliferation and is upregulated in cervical cancer sites, exhibiting apoptosis and dysregulated p53 expression. Furthermore, RBBP6 has been demonstrated to sensitize cancer cells to radiation and certain chemotherapeutic agents by regulating the Bcl-2 gene, thus suggesting a crosstalk among RBBP6/p53/BCL-2 oncogenic signatures. The present study, therefore, investigated the relationship between cisplatin and RBBP6 expression in CC cells. Herein, we first explored bioinformatics simulations and identified that the RBBP6/p53/BCL-2 signaling pathway is overexpressed and correlated with CC. For further analysis, we explored the Genomics of Drug Sensitivity in Cancer (GDSC) and found that most of the CC cell lines are sensitive to CCDP. To validate these findings, RBBP6 was silenced in HeLa and Vero cells using RNAi technology, followed by measurement of wild-type p53 and Bcl-2 at the mRNA level using qPCR. Cells co-treated with cisplatin and siRBBP6 were subsequently analyzed for apoptosis induction and real-time growth monitoring using flow cytometry and the xCELLigence system, respectively. Cancer cells in the cotreatment group showed a reduction in apoptosis compared to the cisplatin-treated group. Moreover, the real-time growth monitoring revealed a reduced growth rate in RBBP6 knockdown cells treated with cisplatin. Although wild-type p53 remained unchanged in the co-treatment group of cancer cells, Bcl-2 was completely repressed, suggesting that RBBP6 is necessary for sensitizing cervical cancer cells to cisplatin treatmen

FAQs

What is the main purpose of the study on RBBP6 in cervical cancer?

To determine how RBBP6 expression and its knockdown influence cisplatin sensitivity in cervical cancer cells.

How was RBBP6 silenced in the experiments?

RBBP6 was silenced in HeLa and Vero cells using RNAi technology (siRBBP6).

What key molecular changes were observed after RBBP6 knockdown with cisplatin?

Bcl-2 was completely repressed, while wild-type p53 remained unchanged, linking cisplatin sensitization to Bcl-2 downregulation.

Sep 21, 2026

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