Moomivand Soraya, Nikbakht Mohsen, Majd Ahmad, Bikhof Torbati Maryam, Mousavi Seyed Asadoullah
Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran.
Research Institute for Oncology, Hematology and Cell Therapy Tehran University of Medical Sciences, Tehran, Iran.
Adv Pharm Bull. 2024 Dec 30;14(4):908-917. doi: 10.34172/apb.42733. Epub 2024 Oct 30.
Autophagy, governed by genes with dual roles in cell death and survival, plays a crucial role in cancer persistence. Arsenic trioxide (ATO), carboplatin (CP), and cyclophosphamide (CY) are used to treat various cancers. ATO impedes cell proliferation and triggers apoptosis in cancer cells. CP, a platinum-based drug, damages cancer cell DNA, while CY acts as an alkylating agent, disrupting cell proliferation. This study investigates the combined effects of ATO, CP, and CY on inducing apoptosis and modulating autophagy in triple-negative breast cancer (TNBC) cell lines, BT-20 and MDA-MB-231.
The cytotoxic effects of ATO, CP, and CY, alone and in combination, were evaluated using the MTT assay on BT-20 and MDA-MB-231 cells. Apoptosis and cell cycle progression were analyzed by annexin-V FITC/PI staining and flow cytometry. Gene expression of autophagy-and apoptosis-related markers, including Beclin 1, LC3, caspase 3, and BCL2, was quantified using RT-PCR. Data were analyzed using GraphPad Prism 4.0 with one-way ANOVA followed by Dunnett's test.
The combination of ATO, CP, and CY significantly reduced cell viability and enhanced apoptosis, evidenced by increased caspase-3 activity and reduced BCL2 expression. Cell cycle arrest in the G1 phase was observed, alongside elevated autophagy markers Beclin 1 and LC3.
The combination of ATO, CP, and CY induces synergistic effects in promoting apoptosis and autophagy in TNBC cell lines. These findings suggest that this combination therapy could be a promising approach to enhancing treatment efficacy in aggressive breast cancers, offering new insights into potential therapeutic strategies.
自噬由在细胞死亡和存活中具有双重作用的基因调控，在癌症持续存在中起关键作用。三氧化二砷（ATO）、卡铂（CP）和环磷酰胺（CY）用于治疗各种癌症。ATO可阻碍癌细胞增殖并触发其凋亡。CP是一种铂类药物，可损伤癌细胞DNA，而CY作为烷化剂，会干扰细胞增殖。本研究调查ATO、CP和CY联合使用对三阴性乳腺癌（TNBC）细胞系BT - 20和MDA - MB - 231诱导凋亡和调节自噬的联合作用。
使用MTT法评估ATO、CP和CY单独及联合使用对BT - 20和MDA - MB - 231细胞的细胞毒性作用。通过膜联蛋白V FITC/PI染色和流式细胞术分析凋亡和细胞周期进程。使用RT - PCR定量自噬和凋亡相关标志物（包括Beclin 1、LC3、半胱天冬酶3和BCL2）的基因表达。数据使用GraphPad Prism 4.0进行分析，采用单因素方差分析，随后进行Dunnett检验。
ATO、CP和CY联合使用显著降低细胞活力并增强凋亡，表现为半胱天冬酶 - 3活性增加和BCL2表达降低。观察到细胞周期停滞在G1期，同时自噬标志物Beclin 1和LC3升高。
ATO、CP和CY联合使用在TNBC细胞系中诱导协同作用，促进凋亡和自噬。这些发现表明这种联合疗法可能是提高侵袭性乳腺癌治疗效果的一种有前景的方法，为潜在治疗策略提供了新的见解。
