期刊
ONCOLOGY LETTERS
卷 5, 期 3, 页码 1010-1016出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2013.1129
关键词
transient receptor potential melastatin 7; midazolam; proliferation; cell cycle arrest; human head and neck carcinoma
类别
资金
- South China Comprehensive Platform for New Medicine RD [2009ZX09301-015]
- Doctoral Fund of the Ministry of Education of China [20100171110050]
- National Natural Science Foundation of China for Young Scholars [81202555]
Transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable channel, has been demonstrated to be present in cancer cells and involved in their growth and proliferation. The present study used midazolam, a benzodiazepine class anesthesic, to pharmacologically intervene in the expression of TRPM7 and to inhibit cancer cell proliferation. Midazolam significantly inhibited the growth and proliferation of FaDu human hypopharyngeal squamous cell carcinoma cells, concurring with the induction of G(0)/G(1) cell cycle arrest and blockage of Rb activation. Central-type and peripheral-type benzodiazepine receptor antagonists did not abrogate proliferation inhibition by midazolam, while the specific TRPM7 agonist bradykinin reversed this effect. In addition, other benzodiazepines, diazepam and clonazepam also exhibited anti-proliferative activities. The inhibitory activity on cancer cell growth and proliferation, combined with the TRPM-dependent mechanism, reveals the anticancer potential of midazolam as a TRPM7 inhibitor and supports the suggestion that TRPM7 is a valuable target for pharmaceutical intervention.
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