Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

BMC Cancer

Mamoru Tanaka¹  Hiromi Kataoka¹  Shigenobu Yano²  Hiromi Ohi⁴  Keisuke Kawamoto³  Takashi Shibahara³  Tsutomu Mizoshita¹  Yoshinori Mori¹  Satoshi Tanida¹  Takeshi Kamiya¹  Takashi Joh¹ 

[1] Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

[2] Office of Society-Academia Collaboration for Innovation, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan

[3] Department of Chemistry, Okayama University of Science, 1-1Ridai-cho, Kita-ku, Okayama, 700-0005, Japan

[4] Department of Industrial Chemistry, Kinki Polytechnic College, 1778 Inaba-cho, Kishiwada, Osaka, 596-0103, Japan

关键词: Gastric cancer;    Drug resistance;    Cisplatin;    Glycoconjugated palladium (II) complex;    Glycoconjugated platinum (II) complex;   

Others  :  1079754
DOI  :  10.1186/1471-2407-13-237

 received in 2012-07-23, accepted in 2013-05-08,  发布年份 2013

【 摘 要 】

Background

Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients.

Methods

We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl₂ (L)] and [PdCl₂ (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl₂ (L)] and [PdCl₂ (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo.

Results

CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl₂ (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl₂ (L)] induced DNA double-strand breaks.

Conclusion

These results indicate that [PdCl₂ (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications.

【 授权许可】

   
2013 Tanaka et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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