Irinotecan

Irinotecan is a topoisomerase inhibitor used primarily for the treatment of colorectal cancer. Irinotecan binds to the topoisomerase I-DNA complex, preventing DNA strand reconnection and leading to DNA double-strand breaks and cell death^[1].

Irinotecan(2μM; 48h) treatment with Panc-1 and MIA PaCa-2 resulted in 57.5% reduction of migratory in Panc-1 cells and in a 53.9% in MIA PaCa-2 cells ^[1]. In the cell cycle analysis, Irinotecan (0.3 to 30μM for 24-48h ) increased the proportions at the S and G2/M phases of cell cycling in parallel with a decreased population at the G1 phase in Caco-2 and CW2 cells ^[2].

For xenografted HCT116 cells, Irinotecan (10mg/kg; i.p; 5days) can reduced tumors by 80% and mice urvival was again improved (>16weeks vs 12weeks in mock ） without any mouse toxicity^[3]. Irinotecan (20mg/kg/day; ip; days 1–3, 8–10) were treat with Prostatic small cell carcinoma (SCC) arrested xenograft growth with a small reduction in tumor volume and only minor weight loss of the hosts (7%)^[4]. Mice given a combination of Irinotecan (50mg/kg; ip; 1,13,19days ) had a decreased number of tumour cells in the peritoneal cavity as compared to non-treated mice but counts on macrophages, lymphocytes and neutrophils were higher than in non-treated mice^[5].

[1]. Rodriguez Lanzi C, Wei R, Luo D, Mackenzie GG. Phospho-Aspirin (MDC-22) inhibits pancreatic cancer growth in patient-derived tumor xenografts and KPC mice by targeting EGFR: Enhanced efficacy in combination with irinotecan. Neoplasia. 2022 Feb;24(2):133-144.
[2]. Kaku Y, Tsuchiya A, Kanno T, Nishizaki T. Irinotecan induces cell cycle arrest, but not apoptosis or necrosis, in Caco-2 and CW2 colorectal cancer cell lines. Pharmacology. 2015;95(3-4):154-9.
[3]. Sharma A, Vatapalli R, Abdelfatah E, Wyatt McMahon K, Kerner Z, A Guzzetta A, Singh J, Zahnow C, B Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2017 Apr 26;12(4):e0176139.
[4]. Tung WL, Wang Y, Gout PW, Liu DM, Gleave M, Wang Y. Use of irinotecan for treatment of small cell carcinoma of the prostate. Prostate. 2011 May 15;71(7):675-81.
[5]. Sharma A, Vatapalli R, Abdelfatah E, Wyatt McMahon K, Kerner Z, A Guzzetta A, Singh J, Zahnow C, B Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2017 Apr 26;12(4):e0176139.

Irinotecan是一种拓扑异构酶抑制剂，主要用于治疗结直肠癌。Irinotecan可通过与拓扑异构酶 I-DNA 复合物结合，阻止 DNA 链的再连接，并导致 DNA 双链断裂和细胞死亡 ^[1]。

Irinotecan（2μM；48h）处理 Panc-1 和 MIA PaCa-2 细胞后，Panc-1 细胞的迁移率降低了 57.5%，MIA PaCa-2 细胞的迁移率降低了 53.9%^[1]。在细胞周期分析中，Irinotecan（0.3 至 30μM；24-48 h）增加了细胞周期 S 期和 G2/M 期的比例，同时减少了 Caco-2 和 CW2 细胞 G1 期的数量^[2]。

对于异种移植的 HCT116 细胞的小鼠，Irinotecan（10mg/kg，po，5days）可使肿瘤缩小 80%，小鼠存活率提高（大于 16 周，模拟小鼠为 12 周），且无任何小鼠毒性^[3]。Irinotecan（20mg/kg/day；ip；第 1-3 天和第 8-10 天）治疗前列腺小细胞癌（SCC）抑制了异种移植的生长，肿瘤体积略有缩小，宿主体重仅轻微下降（7%）^[4]。与未接受治疗的小鼠相比，接受Irinotecan（50mg/kg；ip；1、13、19 天）治疗的小鼠腹腔中肿瘤细胞的数量减少，但巨噬细胞、淋巴细胞和中性粒细胞的数量明显高于未接受治疗的小鼠^[5]。