[Inhibitory effect of CXCR4 blockers on a CXCR4-expressing gastric cancer cell line in nude mice].

Abstract

BACKGROUND AND OBJECTIVE:

CXCR4, one of the chemokine receptors, plays a major role in cell migration in metastasis and cancer dissemination. However, it is not known whether CXCR4 is associated with tumor growth in vivo. In the present study, we investigated the inhibitory effect of CXCR4 blockers on CXCR4-expressing gastric cancer in vivo.

METHODS:

Cells of a CXCR4-expressing gastric cancer cell line, K-MK-2, were transplanted into nude mice. A CXCR4 blocker, AMD3100 (2 mg/kg), was injected and another blocker, KRH3955 (1 mg/kg or 10 mg/kg), was administered orally. Both drugs were administered for 5 days followed by 2 days of rest. The mice were sacrificed on the 35th day following transplantation and the weights of the tumors were measured.

RESULTS:

The mean weights of the tumors were 7.092±1.221 g in the control mice, 5.137±1.001 g in the ADM3100-injected mice, 3.895±2.120 g in mice treated with 1 mg/kg of KRH3955, and 4.257±1.169 g in mice treated with 10 mg/kg of KRH3955. The 2 CXCR4 blockers significantly inhibited the growth of gastric cancer cells transplanted into the nude mice.

CONCLUSION:

The CXCR4 blockers AMD3100 and KRH3955 inhibit tumor growth in vivo. These drugs are possible candidates for personalized therapy of gastric cancer.

• Authors: Tomohiro Iwanaga, Yoshiaki Iwasaki, Manabu Ohashi, Ryoki Ohinata, Keiichi Takahashi, Tatsuro Yamaguchi, Hiroshi Matsumoto, Daisuke Nakano
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 39 Issue 12 Pg. 1788-90 (Nov 2012) ISSN: 0385-0684 [Print] Japan
• PMID: 23267887 (Publication Type: Journal Article)

Chemical References

• Benzylamines
• Cyclams
• Heterocyclic Compounds
• Imidazoles
• N,N-dipropyl-N'-(4-((((1H-imidazol-2-yl)methyl)((1-methyl-1H-imidazol-2-yl) methyl)amino)methyl)benzyl)-N'-methylbutane-1,4-diamine
• Receptors, CXCR4
• plerixafor

Topics

• Animals
• Benzylamines (therapeutic use)
• Cell Line, Tumor
• Cyclams
• Heterocyclic Compounds (therapeutic use)
• Imidazoles (therapeutic use)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Receptors, CXCR4 (antagonists & inhibitors)
• Stomach Neoplasms (drug therapy)
• Xenograft Model Antitumor Assays