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The effects of HAART on the expression of MUC1 and P65 in a cervical cancer cell line, HCS-2
Kutlwano Rekgopetswe Thabethe1, Gbenga Anthony Adefolaju2, Margot Jill Hosie3
1School of Anatomical Sciences, Wits Medical School, University of the Witwatersrand, 7, York Road, Parktown, 2193 Johannesburg, South Africa.
Insights
Highly active antiretroviral therapy (HAART) drugs, particularly protease inhibitors (PIs), show promise in treating cervical cancer. PIs reduced MUC1 and P65 expression, suggesting they may facilitate cancer cell death.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Cervical cancer is a major global health concern and an AIDS-defining malignancy.
- The impact of highly active antiretroviral therapy (HAART) on cervical cancer incidence remains unclear.
- MUC1 and P65 are key signaling molecules implicated in cervical cancer progression.
Purpose of the Study:
- To investigate the effect of HAART drugs on cervical cancer cell lines.
- To analyze the expression of MUC1 and P65 in response to HAART.
- To determine the potential of HAART, specifically protease inhibitors (PIs), as an anticancer treatment.
Main Methods:
- Utilized a cervical cancer cell line (HCS-2) treated with HAART drugs at clinical concentrations.
- Employed real-time quantitative PCR (qPCR) to assess gene expression.
- Used immunofluorescence to evaluate protein expression.
- Statistical analysis performed using one-way ANOVA and Tukey-Kramer post-hoc tests.
Main Results:
- Protease inhibitor (PI) drugs, specifically LPV/r, significantly reduced both MUC1 and P65 gene and protein expression.
- Other tested HAART drugs showed less pronounced effects compared to PIs.
- The reduction in MUC1 and P65 suggests increased susceptibility to cell death in treated cells.
Conclusions:
- HAART drugs, especially PIs, demonstrate anticancer effects against cervical cancer cells.
- PIs may induce cancer cell death by downregulating MUC1 and P65 expression.
- These findings highlight the potential of PIs as therapeutic agents for cervical cancer treatment.
Abstract:
Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24-hour treatment of a cervical cancer cell line, HCS-2, with drugs, which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one-way ANOVA followed by a Tukey-Kramer post-hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death; therefore, the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.
