A novel chemotherapeutic sensitivity-testing system based on collagen gel droplet embedded 3D-culture methods for hepatocellular carcinoma

作者：Hou, Jun; Hong, Zhixian; Feng, Fan; Chai, Yantao; Zhang, Yunkai; Jiang, Qiyu; Hu, Yan; Wu, Shunquan; Wu, Yingsong; Gao, Xunian; Chen, Qiong; Wan, Yong; Bi, Jingfeng^*; Zhang, Zheng^*

来源：BMC Cancer, 2017, 17(1): 729.

DOI：10.1186/s12885-017-3706-6

• Hepatocellular carcinoma
• Multi-drug resistance
• Collagen gel droplet embedded 3D-culture system
• Chemotherapies

Background: Patients suffering from advanced stage hepatocellular carcinoma (HCC) often exhibit a poor prognosis or dismal clinical outcomes due to ineffective chemotherapy or a multi-drug resistance (MDR) process. Thus, it is urgent to develop a new chemotherapeutic sensitivity testing system for HCC treatment. The presence study investigated the potential application of a novel chemotherapeutic sensitivity-testing system based on a collagen gel droplet embedded 3D-culture system (CD-DST).
Methods: Primary cells were separating from surgical resection specimens and then tested by CD-DST. To identify whether HCC cell lines or cells separating from clinical specimens contain MDR features, the cells were treated with an IC50 (half maximal inhibitory concentration) or ICmax (maximal inhibitory concentration) concentration of antitumor agents, e.g., 5-furuolouracil (5-FU), paclitaxel (PAC), cisplatin (CDDP), epirubicin (EPI), or oxaliplatin (L-OHP), and the inhibitory rates (IRs) were calculated.
Results: HepG2 cells were sensitive to 5-FU, PAC, CDDP, EPI, or L-OHP; the IC50 value is 0.83 +/- 0.45 mu g/ml, 0.03 +/- 0. 02 mu g/ml, 1.15 +/- 0.75 mu g/ml, 0.09 +/- 0.03 mu g/ml, or 1.76 +/- 0.44 mu g/ml, respectively. Only eight (8/26), nine (9/26), or five (5/26) patients were sensitive to the ICmax concentration of CDDP, EPI, or L-OHP; whereas only three (3/26), four (4/26), or two (2/26) patients were sensitive to the IC50 concentration of CDDP, EPI, or L-OHP. No patients were sensitive to 5-FU or PAC.
Conclusions: The in vitro drug sensitivity exanimation revealed the MDR features of HCC and examined the sensitivity of HCC cells from clinical specimens to anti-tumor agents. CD-DST may be a useful method to predict the potential clinical benefits of anticancer agents for HCC patients.

• 出版日期2017-11-8
• 单位解放军第302医院; 南方医科大学