TY - JOUR
T1 - Role of myeloid cell leukemia-1 in cell growth of squamous cell carcinoma
AU - Nagata, Masahide
AU - Wada, Koichiro
AU - Nakajima, Atsushi
AU - Nakajima, Noriko
AU - Kusayama, Morio
AU - Masuda, Tomotake
AU - Iida, Seiji
AU - Okura, Masaya
AU - Kogo, Mikihiko
AU - Kamisaki, Yoshinori
PY - 2009/8/3
Y1 - 2009/8/3
N2 - Myeloid cell leukemia-1 (Mcl-1), a member of the B-cell lymphoma-2 (Bcl-2) family, has been reported to be a critical survival factor in hematopoietic cells, yet little data exists for a role of Mcl-1 in human oral squamous cell carcinoma (SCC). A high level expression of Mcl-1 was observed in tumor cells of human primary SCC, lymph node metastasis tissues, and SCC cell lines. We manipulated expression of Mcl-1 protein in SCC cells by small interfering RNA (siRNA) for Mcl-1 and observed that Mcl-1 siRNA inhibited the growth of SCCs accompanied with apoptosis. Combination therapy of Mcl-1 siRNA and anti-tumor drug drastically inhibited the cell growth in comparison to that in each single treatment. In addition, phosphorylation of focal adhesion kinase (FAK) was decreased by treatment with Mcl-1 siRNA, resulting in decreases in phosphorylation of MEK1/2 and MAPK. The cell growth inhibition caused by knockdown of Mcl-1 was suggested to be mainly a result of suppression of proliferation via the inhibition of intracellular FAK/MAPK signaling pathways. These results imply a potentially important and novel role of the inhibition of Mcl-1 function by the use of specific siRNA in the treatment of SCC.
AB - Myeloid cell leukemia-1 (Mcl-1), a member of the B-cell lymphoma-2 (Bcl-2) family, has been reported to be a critical survival factor in hematopoietic cells, yet little data exists for a role of Mcl-1 in human oral squamous cell carcinoma (SCC). A high level expression of Mcl-1 was observed in tumor cells of human primary SCC, lymph node metastasis tissues, and SCC cell lines. We manipulated expression of Mcl-1 protein in SCC cells by small interfering RNA (siRNA) for Mcl-1 and observed that Mcl-1 siRNA inhibited the growth of SCCs accompanied with apoptosis. Combination therapy of Mcl-1 siRNA and anti-tumor drug drastically inhibited the cell growth in comparison to that in each single treatment. In addition, phosphorylation of focal adhesion kinase (FAK) was decreased by treatment with Mcl-1 siRNA, resulting in decreases in phosphorylation of MEK1/2 and MAPK. The cell growth inhibition caused by knockdown of Mcl-1 was suggested to be mainly a result of suppression of proliferation via the inhibition of intracellular FAK/MAPK signaling pathways. These results imply a potentially important and novel role of the inhibition of Mcl-1 function by the use of specific siRNA in the treatment of SCC.
KW - Apoptosis
KW - Human
KW - Myeloid cell leukemia-1 (Mcl-1)
KW - Small interfering RNA (siRNA)
KW - Squamous cell carcinoma
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U2 - 10.1254/jphs.08339FP
DO - 10.1254/jphs.08339FP
M3 - Article
C2 - 19571464
AN - SCOPUS:67749143928
VL - 110
SP - 344
EP - 353
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 3
ER -