Intravenous paclitaxel against metastasis of human gastric tumors of diffuse type.
OBJECTIVE
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((R)) 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.
Tuan
Tsung-Fan
TF
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, Taiwan.
Tsai
Meng-Li
ML
Yeh
Kai-Chia
KC
Huang
Hsin-Chieh
HC
Chung
Cheng-Ta
CT
Huang
Chen-Lung
CL
Han
Chia-Hung
CH
Chen
Ching-Ping
CP
Wang
Min-Hsien
MH
Shen
Chien-Chang
CC
Lai
Yiu-Kay
YK
Lee
Wen-Sen
WS
Hwang
Ling-Ling
LL
Chen
Chiung-Tong
CT
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D010537:Peritoneum / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014162:Transfection
D000972:Antineoplastic Agents, Phytogenic; D049452:Green Fluorescent Proteins; D017239:Paclitaxel