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Intravenous paclitaxel against metastasis of human gastric tumors of diffuse type

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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.

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Acknowledgments

Thanks to Fong-Wen Chen’s assistance in the invasion studies. The study was supported by grants NHRI-BP-095-PP07 and NHRI-BP-097-PP07 from The National Health Research Institutes, Taiwan, and NSC 94-2213-E-400-001 from The National Science Council, Taiwan.

Conflict of interest statement

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Authors and Affiliations

  1. Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan

    Tsung-Fan Tuan, Kai-Chia Yeh, Hsin-Chieh Huang, Cheng-Ta Chung, Chen-Lung Huang, Chia-Hung Han, Ching-Ping Chen, Min-Hsien Wang, Chien-Chang Shen, Ling-Ling Hwang & Chiung-Tong Chen

  2. Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Sinyi, Taipei, 11031, Taiwan

    Tsung-Fan Tuan, Wen-Sen Lee, Ling-Ling Hwang & Chiung-Tong Chen

  3. Department of Biomechatronic Engineering, National Ilan University, Ilan, Taiwan

    Meng-Li Tsai

  4. Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan

    Cheng-Ta Chung & Yiu-Kay Lai

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  1. Tsung-Fan Tuan
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Correspondence to Ling-Ling Hwang or Chiung-Tong Chen.

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Tuan, TF., Tsai, ML., Yeh, KC. et al. Intravenous paclitaxel against metastasis of human gastric tumors of diffuse type. Cancer Chemother Pharmacol 66, 773–783 (2010). https://doi.org/10.1007/s00280-009-1222-3

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