Health Science Reviews

By Zinhle Radebe

For millions of women worldwide, cervical cancer remains a threat. It ranks as the fourth most common cancer among women globally. While treatments like radiotherapy help treat cancer at all stages and reduce mortality, they are not always effective because cancer cells can develop resistance, making them harder to eliminate. Recent studies have investigated whether vitamin D could enhance the sensitivity of cervical cancer to radiation. Vitamin D exists in two forms: ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃), produced in the skin upon exposure to UVB rays and sourced from diet. It has been known for its role in immune and bone health. Recently, it has been shown to regulate genes involved in apoptosis, cell cycle arrest, and differentiation through the vitamin D receptor (VDR).

A study by Zhang, Yu, and Cheng (2025) identified vitamin D as a radiosensitizer; this research was conducted both in vivo and in vitro. Cervical cancer cell lines (SiHa and CasKi) and mouse models with implanted cervical cancer tumors were treated with vitamin D, radiation alone, or both. Cell survival and death were assessed using colony-forming assays and Trypan blue staining. In vitro, the combination of vitamin D and radiation significantly decreased cancer cell survival compared to radiation alone. In mouse models, the combined therapy reduced tumor growth relative to the control and had minimal impact on the mice’s body weight, with no noticeable changes in their major organs. The study also performed mechanism analysis using proteomics, Western blot, flow cytometry, qPCR, electron microscopy, and autophagy inhibitors to show how vitamin D helps sensitize cancer cells to radiation and prevents resistance by inhibiting autophagy through downregulation of Ambra 1, a key regulator of autophagy, while promoting apoptosis through upregulation of caspase 8, an enzyme involved in programmed cell death. Not only did vitamin D improve the efficacy of radiation, but it also reduced toxicity in the treated mouse models, which showed no weight loss or organ damage, indicating a safe profile. This research is important because it identified a radiosensitizer with the potential to become an adjuvant therapy, making cancer cells more responsive to radiation and improving treatment outcomes. Vitamin D is a low-cost, easily accessible, and low-risk adjuvant to radiotherapy.

Although this study presents promising possibilities, it also has limitations, such as the lack of human clinical data. The research was conducted only using cell lines and mouse models, making it uncertain whether these results will translate to humans. The effect might only be relevant to specific cervical subtypes, as only two cell lines were tested. Tumour growth and response were monitored over a short period, and long-term effects, recurrence, or metastasis were not assessed. While the findings are promising, further research involving humans and a wider range of tumour models is necessary before considering clinical application. Vitamin D could enhance cervical cancer treatment by increasing the efficacy of radiation therapy and reducing side effects.

References

1. Zhang, Z., Yu, X. and Cheng, G. (2025). Vitamin D sensitizes cervical cancer to radiation-induced apoptosis by inhibiting autophagy through degradation of Ambra1. Cell Death Discovery, 11(1). doi:https://doi.org/10.1038/s41420-024-02279-7.
2. Deeb, K.K., Trump, D.L. and Johnson, C.S. (2007). Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Reviews Cancer, 7(9), pp.684–700. doi:https://doi.org/10.1038/nrc2196.