Akademik Veri Yönetim Sistemi
Cellular Bases for Patient Response to Cancer Therapies, Lyon, Fransa, 14 - 16 Kasım 2023, ss.3
Background: Triple negative breast cancer (TNBC) is the lack of survival subtype and treatment options are limited due to resistance to chemotherapy. Therefore, new drug discoveries and alternative therapies are needed for the treatment of TNBC. Irinotecan (Ir) is an effective chemotherapeutic agent used in various cancer treatments. SN38, the active metabolite of Ir, binds to the topoisomerase I-DNA complex, causing double strand breaks. SN38 has some limitations in therapy, including its instability in physiological circulation, short half-life, low metabolism and toxicity. Therefore, there is a need for structural modification of SN38 and increasing its activity. The present study aimed to increase the encapsulation efficiency and short half-life of SN38 by forming a lipophilic prodrug (LIPoSN38-OA) by attaching oleic acid (OA) to the carbon at the C10 position. Method: SN38-OA was modified by ester synthesis and characterized by NMR, FTIR, UV-VIS. SN38-OA was encapsulated by thin film method and characterized by UV-VIS, Zeta, TEM measurements. The effects of LiposSN38 and LipoSN38- OA on MDA-MB-231 and MCF10A cells were analyzed by MTT, AO/EtBr, Annexin V, cell cycle and scratch assay. Results: LipoSN38-OA was 90% encapsulated and showed a low dose IC50 value (25nM*p<0.05) compared to SN38 (48 h) at effective time. Compared to SN38 and SN38-OA, LipoSN38-OA inhibited cell viability by 80%, while no statistically significant toxic effect was observed in healthy cells. SN38, SN38-OA, LipoSN38, LipoSN38-OA increased the apoptotic cell rate from 5.39% to 32.79%, 45.37%, 17.16% 20.12%, respectively compared to control. Additionally, LipoSN38-OA combination induced a different type of death accompanied by apoptosis. LipoSN38-OA induced cell arrest in the G2/M phase and inhibited cell migration by approximately 80% (*p<0.001). Conclusion: LipoSN38-OA increases the bioavailability of SN38 and may be a promising and effective potential anticancer agent in the treatment of TNBC.