[The combination of octreotide to rofecoxib enhanced the inhibitory effect on growth of human hepatocellular carcinoma].
OBJECTIVE
To know whether octreotide combined with rofecoxib would enhance the inhibitory effect on proliferation of hepatocellular carcinoma (HCC) in vitro and in vivo.


METHODS
The proliferation of HCC SMMC 7721 cells were measured by incorporating (3)H-thymidine ribotide ((3)H-TdR) into DNA. The effect of octreotide combined with rofecoxib on proliferation of HCC cells was evaluated according to the median-response principle. SMMC-7721 cells were implanted orthotopically in the liver of nude mice. Nude mice were treated with either octreotide (100 micro g x kg(-1) x d(-1)) combined with rofecoxib (30 mg x kg(-1) x d(-1)) or rofecoxib (30 mg x kg(-1) x d(-1)) alone for 8 weeks. The volumes of implanted tumors were measured.


RESULTS
The combination of octreotide and rofecoxib significantly inhibited (3)H-TdR incorporation of HCC cell line in culture in a dose-dependent manner (r = -0.997, P < 0.01). The combination indexes of octreotide and rofecoxib in the majority of effect range were less than 1. The inhibitory rate of xenograft in situ in the combined group (97.1%) was significantly higher than that in the rofecoxib group (73.2%). In addition, increased amount of fibroplasia was observed in the combined group as compared with that in control group. No severe side effect was observed in all the treatment groups.


CONCLUSIONS
The inhibitory effect of octreotide combined with rofecoxib on HCC cell line was significantly greater than that of octreotide or rofecoxib alone in vitro. Octreotide combined with rofecoxib greatly enhanced the anti-growth effects on HCC in vivo when compared with rofecoxib alone. These synergic results may be of potential therapeutic benefit to those patients with non-resectable HCC.
Liu
Chun-lun
CL
Department of Gastroenterology, The First Hospital, Chongqing Medical University, Chongqing 400016, China.
Tang
Cheng-wei
CW
Zhou
Xu-chun
XC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000494:pharmacology*; D013450:Sulfones; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D015282:Octreotide