Effects of paclitaxel and doxorubicin in histocultures of hepatocelular carcinomas.
Cancer has been the leading cause of death in Taiwan over the past two decades and liver cancer is the leading cause of all cancer deaths in Taiwan with a trend of increase in incidence. Therapeutic options and efficacy for liver cancer have been limited and the 5-year survival rate is less than 7% in the Unite States. The study was conducted to establish a histoculture system of human hepatocellular carcinomas (HCC) for biological and pharmacological studies and to determine the efficacy of anticancer drugs with the established HCC histocultures. Patient HCC tissues freshly obtained after surgeries were prepared and histocultured. The histocultured HCC were treated with doxorubicin and paclitaxel of various concentrations for 96-h. Upon drug treatments, the activity of tumor cell proliferation and extent of cell death induction were measured and changes of the alpha-fetoprotein levels in the culture medium were determined. We demonstrated that human HCC can be successfully cultured in a 3-dimensional histoculture system and used for pharmacological studies. Doxorubicin and paclitaxel showed concentration-dependent activities in anti-proliferation and cell death induction against the human HCC. Inhibitory effects of both drugs on alpha-fetoprotein production of the cultured HCC were in agreement with their anti-proliferative effects. Exposure time-dependent antitumoral effects of paclitaxel treatments at 3-, 24-, and 96-h against the histocultured HCC PLC/PRF/5 xenograft tumors were also observed. In conclusion, we have demonstrated a histoculture system for patient HCC and it can be utilized in selection of active drugs prior to treatments in patients and in evaluation of new agents against HCC, for which therapeutic agents are in desperate needs worldwide.
Chuu
Jiunn-Jye
JJ
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan.
Liu
Jacqueline Ming
JM
Tsou
Mei-Hua
MH
Huang
Chen-Lung
CL
Chen
Ching-Ping
CP
Wang
Hsin-Sheng
HS
Chen
Chiung-Tong
CT
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000378:metabolism
D000970:Antineoplastic Agents; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D000509:alpha-Fetoproteins