Endometrial cancer is the most common gynaecological pathology and is the sixth most common cancer in women worldwide, with an estimated 417,000 diagnoses in 2020. The disease incidence has increased by 132 percent over the last 30 years and is speculated to rise due to an ageing population and surging worldwide prevalence of obesity and diabetes. [1] Most notably, the 5-year survival rate has declined significantly over the past 30 years, this makes endometrial cancer one of only two cancers with rising mortality rates. [2] For patients with early-stage disease, hysterectomy is considered a definitive treatment. In contrast, advanced-stage and high-grade endometrial cancers are fatal. This is due to chemotherapy resistance and metastasis. Nevertheless, new therapies are being tested, aiming to improve treatment efficacy and patient outcomes, such as targeted therapies, immunotherapy, and hormone therapy, either alone or in combination. [3]
The aim of this study was to investigate the combination of epigenetic inhibitors and cannabidiol potential for endometrial cancer treatment in comparison to standard chemotherapy. The endometrium KLE cell line was treated with sodium butyrate, EGCG, BML-210, zebularine, cannabidiol, paclitaxel and cisplatin. We prepared cell growth analysis with Trypan Blue, apoptosis and cell cycle analysis with Propidium Iodide, gene expression analysis with quantitative Polymerase Chain Reaction, and protein analysis with Western Blot. We observed that combination of cannabidiol with HDACi or DNMTi reduced viability of the cells and increased apoptosis. Moreover, we discovered changes in the expression of genes responsible for actin cytoskeleton regulation, cell cycle, apoptosis, decidualization, genes critical in epigenetic regulation (DNMT1, DNMT3A, DNMT3B, HDAC1, EED, SUZ12, EHMT2) and in immune response.
In conclusion, the combination of epigenetic inhibitors and cannabidiol increases apoptosis and reduces proliferation. These findings provide new insights into the potential of combining cannabinoids with epigenetic therapy as an alternative approach for endometrial cancer treatment, warranting further investigation into its clinical applicability.