title: Combination chemotherapy of doxorubicin and paclitaxel for hepatocellular carcinoma in vitro and in vivo.
abstract: OBJECTIVE
  Systemic combination chemotherapy is the only option for patients with unresectable hepatocellular carcinoma (HCC) not suitable for intra-arterial treatment. However, no systemic chemotherapy has been able to provide durable remission. The search for a new combination of drugs for HCC is significant. The combination of doxorubicin and paclitaxel shows promise in breast cancer therapy. This study was carried out to determine the synergistic effect of combined doxorubicin and paclitaxel in the two HCC cell lines: HepG2 and Huh7 in vitro and murine HCC H22-bearing BALB/c mice in vivo.
  
  
  METHODS
  The morphology of the two cell lines treated with drugs was photomicrographed. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay was used to determine the number of surviving cells. Cell cycle was evaluated by flow cytometry. Cell viability was measured by the ability of single cells to form colonies in vitro. Anti-tumor activities against subcutaneoulsy implanted solid tumor induced by H22 cells in mice were evaluated.
  
  
  RESULTS
  Our data demonstrated that the cytotoxicity produced by doxorubicin and paclitaxel was additive in HCC cells, while it was mainly held in the G2/M phase of the cell cycle by paclitaxel. In vivo anti-tumor activity assay also showed that the combination of the two drugs resulted in more significant tumor regression, compared to the single one.
  
  
  CONCLUSIONS
  The study may provide a new combination of cytotoxic drugs for HCC chemotherapy.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
authors.forename: Haimin
authors.initials: H
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Ling
authors.initials: L
authors.lastname: Bai
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Cao
authors.forename: Wenjie
authors.initials: W
authors.lastname: Song
authors.forename: Kefeng
authors.initials: K
authors.lastname: Dou
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D017239:Paclitaxel
references.citation: J Clin Oncol. 1994 Jun;12(6):1204-11
references.pmid: 8201383
references.citation: J Natl Cancer Inst. 2005 Oct 19;97(20):1532-8
references.pmid: 16234567
references.citation: Chin Med J (Engl). 2008 Oct 20;121(20):1975-9
references.pmid: 19080259
references.citation: J Hepatol. 1990 Sep;11(2):181-4
references.pmid: 2174933
references.citation: N Engl J Med. 1995 May 11;332(19):1256-61
references.pmid: 7708069
references.citation: J Natl Cancer Inst Monogr. 1993;(15):141-7
references.pmid: 7912520
references.citation: Cancer Chemother Pharmacol. 2008 Apr;61(5):847-53
references.pmid: 17609947
references.citation: J Clin Oncol. 2008 Apr 20;26(12):1980-6
references.pmid: 18421049
references.citation: Surg Oncol Clin N Am. 2003 Jan;12(1):127-34
references.pmid: 12735134
references.citation: Am J Clin Oncol. 2006 Jun;29(3):267-75
references.pmid: 16755180
references.citation: Gut. 2002 Oct;51(4):459-62
references.pmid: 12235060
references.citation: Semin Oncol. 2001 Oct;28(5):514-20
references.pmid: 11685744
references.citation: Hepatogastroenterology. 2005 Jul-Aug;52(64):1083-6
references.pmid: 16001634
references.citation: Cancer Treat Rev. 1988 Mar;15(1):1-31
references.pmid: 2834053
references.citation: World J Gastroenterol. 2003 Apr;9(4):696-700
references.pmid: 12679913
references.citation: Transplant Proc. 2005 Mar;37(2):1254-6
references.pmid: 15848687
references.citation: Oncol Rep. 2007 May;17(5):1195-200
references.pmid: 17390065
references.citation: Expert Opin Investig Drugs. 2004 Dec;13(12):1555-68
references.pmid: 15566313
references.citation: Nat Genet. 2002 Aug;31(4):339-46
references.pmid: 12149612
references.citation: Eur J Cancer. 1998 Jul;34(8):1290-2
references.pmid: 9849493
references.citation: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references.pmid: 15761078
references.citation: Chin Med J (Engl). 2005 Oct 20;118(20):1688-94
references.pmid: 16313753
references.citation: Transplant Proc. 2002 Sep;34(6):2316-7
references.pmid: 12270414
references.citation: Lancet. 2003 Dec 6;362(9399):1907-17
references.pmid: 14667750
references.citation: Int J Radiat Oncol Biol Phys. 1998 Feb 1;40(3):583-92
references.pmid: 9486608
references.citation: Ann Surg. 1993 Apr;217(4):375-84
references.pmid: 8385442