Intravenous paclitaxel against metastasis of human gastric tumors of diffuse type

Tsung Fan Tuan, Meng Li Tsai, Kai Chia Yeh, Hsin Chieh Huang, Cheng Ta Chung, Chen Lung Huang, Chia Hung Han, Ching Ping Chen, Min Hsien Wang, Chien Chang Shen, Yiu Kay Lai, Wen-Sen Lee, Ling-Ling Hwang, Chiung Tong Chen

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Purpose: Gastric cancer is one of the leading cancerous diseases worldwide. It is diagnosed often at the advanced stage for which chemotherapy is the main treatment option. The prognosis remains poor for metastatic, especially the diffuse type, gastric cancers. We investigated the efficacy of intravenously administered paclitaxel treating metastases of locally disseminated gastric tumors of diffuse type. Methods: Transfection of green fluorescent proteins (GFP)-expressing plasmid into human gastric cancer MKN45 cells of diffuse type was performed, and MKN45-GFP cells constitutively expressing GFP were isolated. The MKN45-GFP cells were orthotopically inoculated into the mouse peritoneal cavity, and tumor growth and organ metastases were monitored. Liver metastases were harvested, re-inoculated, monitored for liver metastases again, and harvested for further inoculation. This in vivo selection procedure was repeated to isolate a subline with high metastatic abilities demonstrated by in vitro invasion abilities using Transwell® system. By visualizing the GFP-expressing tumors, the effects of intravenously administered paclitaxel against the growing peritoneally disseminated and metastasized tumors in nude mice without laparotomy were measured. Results: An in vivo selected gastric cancer cell line MKN45-GFP-ip4 with high metastatic ability was established. Its invasion ability was inhibited by paclitaxel treatments in vitro. The growths of metastatic and intraperitoneally disseminated MKN45-GFP-ip4 tumors were significantly suppressed by intravenous paclitaxel treatments in nude mice. Conclusions: We found that intravenous paclitaxel is active against the metastases of human gastric cancer of peritoneal diffuse type, which warrants further investigations on optimizing the perioperative regimens with intravenous paclitaxel therapy for gastric cancer in patients.

Original languageEnglish
Pages (from-to)773-783
Number of pages11
JournalCancer Chemotherapy and Pharmacology
Volume66
Issue number4
DOIs
Publication statusPublished - Sept 2010

Keywords

  • Chemotherapy
  • Metastasis
  • Paclitaxel
  • Stomach
  • Taxol

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Oncology
  • Cancer Research
  • Toxicology
  • Pharmacology

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