Pascale Florentina, Bedouet Laurent, Baylatry Mintham, Namur Julien, Laurent Alexandre
ArchimMed, Jouy-en-Josas, France Interventional Imaging Center, Paris Hospitals and Healthcare Organisation, Jouy-en-Josas, France
Occlugel, Jouy-en-Josas, France.
Anticancer Res. 2015 Dec;35(12):6497-503.
To compare the cytotoxic effects of 11 anticancer agents against VX2 and HepG2 cells in order to establish candidate drugs that can be tested preclinically on VX2 tumor model for transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC).
VX2 and HepG2 cells were incubated with different drug concentrations. The half-maximal inhibitory concentration (IC50) values were determined by total cell protein assay for anthracyclines, platins, irinotecan, mytomicin-C (MMC), 5-fluorouracil (5-FU) and antiangiogenics.
IC50 values for VX2 and HepG2 were found close for doxorubicin (0.8 μM vs. 1.1 μM), MMC (13.9 μM vs. 8.7 μM), sunitinib (32.7 vs. 33.7 μM), sorafenib (10.3 vs. 8.9 μM), lapatinib (30 vs. 18.3 μM) and different for platins and irinotecan. Oxaliplatin was less active against VX2 than HepG2 (IC50=41 μM vs. 2.7 μM), cisplatin was more active against VX2 than HepG2 (IC50=8.0 μM vs. 15.9 μM), whereas carboplatin had a low toxicity against both cell lines (70.4 μM vs. 538.3 μM). The toxicity of 5-FU against VX2 and HepG2 was low (IC50=560.6 μM vs. 323.2 μM). Irinotecan was less active against VX2 vs. HepG2 (IC50=44.5 μM vs. 15.3 μM). Bevacizumab had no effect on either of the cell lines up to 6.7 μM.
Drugs recommended for pre-clinical trials of TACE in the VX2 model are doxorubicin, sunitinib, sorafenib, MMC, lapatinib and 5-FU.
比较11种抗癌药物对VX2细胞和HepG2细胞的细胞毒性作用，以确定可在VX2肿瘤模型上进行临床前测试用于肝细胞癌（HCC）经动脉化疗栓塞（TACE）的候选药物。
将VX2细胞和HepG2细胞与不同药物浓度孵育。通过总细胞蛋白测定法确定蒽环类药物、铂类、伊立替康、丝裂霉素-C（MMC）、5-氟尿嘧啶（5-FU）和抗血管生成药物的半数最大抑制浓度（IC50）值。
发现阿霉素对VX2细胞和HepG2细胞的IC50值相近（0.8 μM对1.1 μM），MMC（13.9 μM对8.7 μM），舒尼替尼（32.7对33.7 μM），索拉非尼（10.3对8.9 μM），拉帕替尼（30对18.3 μM），而铂类和伊立替康的IC50值不同。奥沙利铂对VX2细胞的活性低于HepG2细胞（IC50 = 41 μM对2.7 μM），顺铂对VX2细胞的活性高于HepG2细胞（IC50 = 8.0 μM对15.9 μM），而卡铂对两种细胞系的毒性均较低（70.4 μM对538.3 μM）。5-FU对VX2细胞和HepG2细胞的毒性较低（IC50 = 560.6 μM对323.2 μM）。伊立替康对VX2细胞的活性低于HepG2细胞（IC50 = 44.5 μM对15.3 μM）。贝伐单抗在浓度高达6.7 μM时对两种细胞系均无影响。
推荐用于VX2模型TACE临床前试验 的药物有阿霉素、舒尼替尼、索拉非尼、MMC、拉帕替尼和5-FU。
