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

Abstract

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 IC ₅₀ (half maximal inhibitory concentration) or IC _max (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 IC ₅₀ value is 0.83 ± 0.45 μg/ml, 0.03 ± 0.02 μg/ml, 1.15 ± 0.75 μg/ml, 0.09 ± 0.03 μg/ml, or 1.76 ± 0.44 μg/ml, respectively. Only eight (8/26), nine (9/26), or five (5/26) patients were sensitive to the IC _max concentration of CDDP, EPI, or L-OHP; whereas only three (3/26), four (4/26), or two (2/26) patients were sensitive to the IC ₅₀ 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.