Treatment for chemotherapy

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One of the main components of chemotherapy combination regimens used to treat colorectal cancer (CRC) is 5-fluorouracil (5-FU); however, this regimen is associated with serious side effects and chemoresistance. To solve these issues and raise the patient survival rate, it is necessary to create more effective CRC treatment methods. Current research on colon carcinogenesis has focused more on 17-estradiol (E2), which dramatically reduces the incidence of CRC in females of reproductive age as compared to males of the same age. The purpose of this study was to compare how human HT-29 female and SW480 male primary CRC cells responded to E2 and/or 5-FU single or dual therapy for cell cycle progression and apoptosis to SW620 male metastatic CRC cells. The IC50 concentrations of E2 (10 nM) and 5-FU (50 M), either alone or in combination (E+F), were administered to the HT-29, SW480, and SW620 cells for 48 hours before flow cytometry was used to analyse the cell cycle and apoptosis. The purpose of this study was to compare how human HT-29 female and SW480 male primary CRC cells responded to E2 and/or 5-FU single or dual therapy for cell cycle progression and apoptosis to SW620 male metastatic CRC cells. The IC50 concentrations of E2 (10 nM) and 5-FU (50 M), either alone or in combination (E+F), were administered to the HT-29, SW480, and SW620 cells for 48 hours before flow cytometry was used to analyse the cell cycle and apoptosis.  This study is the first to show that the anti-cancer effects of 17-estradiol and 5-fluorouracil dual therapy were superior to the monotherapies in female and male primary CRC cells. It is suggested that this treatment approach may be effective for the earliest stages of CRC. However, 17-estradiol monotherapy may be a more effective strategy for treating the disease's metastatic forms. However, further research is still needed to pinpoint their precise therapeutic benefits in CRC.

From Sigma-Aldrich Co., the 17-estradiol (E2) (E8875-5G) was purchased (St. Louis, MO, USA).The chemotherapeutic drug 5-Fluorouracil (5-FU) was purchased from Hospira Australia Ltd. (Melbourne, Australia).Additionally, Thermo Fisher Scientific provided all of the cell culture supplies, such as Dulbecco's Modified Eagle's Media (DMEM) (#10566032), foetal bovine serum (FBS) (#A3160802), and antibiotic-antimycotic solution (#15240062). (Waltham, MA, USA).

The American Type Culture Collection was used to obtain human female (HT-29), male (SW480), and metastatic male (SW620) colon cancer cell lines (ATCC; Manassas, VA, USA).At 37 °C and 5% CO2, the cells were grown in DMEM with 10% FBS and 1% antibiotic-antimycotic solution added. The previous publication provided more details regarding the characteristics of these chosen cells in connection to their endogenous expression of oestrogen receptors (ER and/or ER).

 The IC50 was calculated using the 3-(4,5-176 Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) cytotoxicity assay after the colon cancer cells were first exposed to a range of E2 and 5-FU doses for 72 hours. In particular, the IC50 values for the E2 were 11.7 M, 12 M, and 12.5 M for the HT-29 cells, and the IC50 values for the 5-FU were 50.7 M, 54.2 M, and 66.9 M, respectively, for the SW480 cells, SW480 cells, and SW620 cells. It is evident from the MTT data that the colon cancer cells exhibit a nearly identical dosage response in terms of cell viability inhibition and IC50 values examined in terms of cell death, specifically the apoptosis type, and cell cycle. Untreated control (CT), E2 and 5-FU monotherapies, and dual combination therapy (E+F) were the treatment groups. All treatments were carried out in triplicate across three separate experiments (n = 3).