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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

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

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

Published in: BMC Cancer | Issue 1/2017

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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.
Literature
1.
Wang C, Wang H, Yang W, Hu K, Xie H, Hu KQ, Bai W, Dong Z, Lu Y, Zeng Z, Lou M, Wang H, Gao X, Chang X, An L, Qu J, Li J, Yang Y. Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma. Hepatology. 2015;61:1579–90.CrossRefPubMed
2.
3.
Tang R, Liu H, Yuan Y, Xie K, Xu P, Liu X, Wen J. Genetic factors associated with risk of metabolic syndrome and hepatocellular carcinoma. Oncotarget. 2017;8:35403–11.PubMedPubMedCentral
4.
He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, Frazer KA, Harismendy O, Hatziapostolou M, Iliopoulos D, Suetsugu A, Hoffman RM, Tateishi R, Koike K, Karin M. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell. 2013;155:384–96.CrossRefPubMedPubMedCentral
5.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China 2015. CA Cancer J Clin. 2016;66:115–32.CrossRefPubMed
6.
Jeong S, Cheng Q, Huang L, Wang J, Sha M, Tong Y, Xia L, Han L, Xi Z, Zhang J, Kong X, Gu J, Xia Q. Risk stratification system to predict recurrence of intrahepatic cholangiocarcinoma after hepatic resection. BMC Cancer. 2017;17:464.CrossRefPubMedPubMedCentral
7.
8.
Jia H, Yang Q, Wang T, Cao Y, Jiang QY, Ma HD, Sun HW, Hou MX, Yang YP, Feng F. Rhamnetin induces sensitization of hepatocellular carcinoma cells to a small molecular kinase inhibitor or chemotherapeutic agents. Biochim Biophys Acta. 1860;2016:1417–30.
9.
Geschwind JF, Gholam PM, Goldenberg A, Mantry P, Martin RC, Piperdi B, Zigmont E, Imperial J, Babajanyan S, Foreman PK, Cohn A. Use of Transarterial Chemoembolization (TACE) and Sorafenib in patients with Unresectable Hepatocellular carcinoma: US regional analysis of the GIDEON registry. Liver Cancer. 2016;5:37–46.CrossRefPubMed
10.
Chen Y, Feng F, Gao X, Wang C, Sun H, Zhang C, Zeng Z, Lu Y, An L, Qu J, Wang F, Yang Y. MiRNA153 reduces effects of chemotherapeutic agents or small molecular Kinase inhibitor in HCC cells. Curr Cancer Drug Targets. 2015;15:176–87.CrossRefPubMed
11.
Takamura Y, Kobayashi H, Taguchi T, Motomura K, Inaji H, Noguchi S. Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers. Int J Cancer. 2002;98(3):450–5.CrossRefPubMed
12.
Miyazaki R, Anayama T, Hirohashi K, Okada H, Kume M, Orihashi K. In vitro drug sensitivity tests to predict molecular target drug responses in surgically Resected lung cancer. PLoS One. 2016;11:e0152665.CrossRefPubMedPubMedCentral
13.
Higashiyama M, Oda K, Okami J, Maeda J, Kodama K, Imamura F, Minamikawa K, Takano T, Kobayashi H. Prediction of chemotherapeutic effect on postoperative recurrence by in vitro anticancer drug sensitivity testing in non-small cell lung cancer patients. Lung Cancer. 2010;68:472–7.CrossRefPubMed
14.
Sun P, Xu Y, DU X, Ning N, Sun H, Liang W, Li R. An engineered three-dimensional gastric tumor culture model for evaluating the antitumor activity of immune cells in vitro. Oncol Lett. 2013;5:489–94.PubMed
15.
Lin Y, Lv F, Liu F, Guo X, Fan Y, Gu F, Gu J, Fu L. High expression of Pyruvate Kinase M2 is associated with Chemosensitivity to Epirubicin and 5-fluorouracil in breast cancer. J Cancer. 2015;6:1130–9.CrossRefPubMedPubMedCentral
16.
Takahashi K, Hosokawa M, Kasajima H, Hatanaka K, Kudo K, Shimoyama N, Miyashita K. Anticancer effects of fucoxanthin and fucoxanthinol on colorectal cancer cell lines and colorectal cancer tissues. Oncol Lett. 2015;10:1463–7.PubMedPubMedCentral
17.
Yoshioka Y, Tsutsumi Y, Kamada H, Kihira T, Tsunoda S, Yamamoto Y, Okamoto T, Shibata H, Mukai Y, Taniai M, Shimizu T, Kawamura M, Abe Y, Nakagawa S, Mayumi T. Selective enhancer of tumor vascular permeability for optimization of cancer chemotherapy. Biol Pharm Bull. 2004;27:437–9.CrossRefPubMed
18.
Shrum B, Costello P, McDonald W, Howlett C, Donnelly M, McAlister VC. In vitro three dimensional culture of hepatocellular carcinoma to measure prognosis and responsiveness to chemotherapeutic agents. Hepatobiliary Surg Nutr. 2016;5:204–8.CrossRefPubMedPubMedCentral
19.
Zhu M, Li M, Wang T, Linghu E, Wu B. MicroRNA-137 represses FBI-1 to inhibit proliferation and in vitro invasion and migration of hepatocellular carcinoma cells. Tumour Biol. 2016;37:13995–4008.CrossRefPubMed
20.
Zhong JH, Peng NF, You XM, Ma L, Xiang X, Wang YY, Gong WF, Wu FX, Xiang BD, Li L. Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: a real-world study. Oncotarget. 2017;8:18296–302.PubMedPubMedCentral
21.
Liu F, Wang G, Wang X, Che Z, Dong W, Guo X, Wang Z, Chen P, Hou D, Zhang Q, Zhang W, Pan Y, Yang D, Liu H. Targeting high aurora kinases expression as an innovative therapy for hepatocellular carcinoma. Oncotarget. 2017;8:27953–65.PubMedPubMedCentral
22.
Cheng Y, Luo R, Zheng H, Wang B, Liu Y, Liu D, Chen J, Xu W, Li A, Zhu Y. Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular carcinoma. Oncotarget. 2017;8:23265–76.PubMedPubMedCentral
23.
Tong Y, Li Z, Liang Y, Yu H, Liang X, Liu H, Cai X. Postoperative adjuvant TACE for patients of hepatocellular carcinoma in AJCC stage I: friend or foe? A propensity score analysis. Oncotarget. 2017;8:26671–8.PubMedPubMedCentral
24.
Kobayashi H, Tanisaka K, Doi O, Kodama K, Higashiyama M, Nakagawa H, Miyake M, Taki T, Hara S, Yasutomi M, Hanatani Y, Kotake K, Kubota T. An in vitro chemosensitivity test for solid human tumors using collagen gel droplet embedded cultures. Int J Oncol. 1997;11(3):449–55.PubMed
25.
Zeng Z, Ren J, O'Neil M, Zhao J, Bridges B, Cox J, Abdulkarim B, Schmitt TM, Kumer SC, Weinman SA. Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation. BMC Cancer. 2012;12:584.CrossRefPubMedPubMedCentral
26.
Terazawa T, Kondo S, Hosoi H, Morizane C, Shimizu S, Mitsunaga S, Ikeda M, Ueno H, Okusaka T. Transarterial infusion chemotherapy with cisplatin plus S-1 for hepatocellular carcinoma treatment: a phase I trial. BMC Cancer. 2014;14:301.CrossRefPubMedPubMedCentral
27.
Zhu M, Li W, Lu Y, Dong X, Chen Y, Lin B, Xie X, Guo J, Li M. Alpha fetoprotein antagonizes apoptosis induced by paclitaxel in hepatoma cells in vitro. Sci Rep. 2016;6:26472.CrossRefPubMedPubMedCentral
28.
Zhao J, Bai Z, Feng F, Song E, Du F, Zhao J, Shen G, Ji F, Li G, Ma X, Hang X, Xu B. Cross-talk between EPAS-1/HIF-2α and PXR signaling pathway regulates multi-drug resistance of stomach cancer cell. Int J Biochem Cell Biol. 2016;72:73–88.CrossRefPubMed
29.
Cerezo D, Ruiz-Alcaraz AJ, Lencina-Guardiola M, Cánovas M, García-Peñarrubia P, Martínez-López I, Martín-Orozco E. Attenuated JNK signaling in multidrug-resistant leukemic cells. Dual role of MAPK in cell survival. Cell Signal. 2017;30:162–70.CrossRefPubMed
30.
Zhu YJ, Zheng B, Wang HY, Chen L. New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacol Sin. 2017;38:614–22.CrossRefPubMed
Metadata
Title
A novel chemotherapeutic sensitivity-testing system based on collagen gel droplet embedded 3D–culture methods for hepatocellular carcinoma
Authors
Jun Hou
Zhixian Hong
Fan Feng
Yantao Chai
Yunkai Zhang
Qiyu Jiang
Yan Hu
Shunquan Wu
Yingsong Wu
Xunian Gao
Qiong Chen
Yong Wan
Jingfeng Bi
Zheng Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3706-6

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