Chemoresistance to concanamycin A1 in human oral squamous cell carcinoma is attenuated by an HDAC inhibitor partly via suppression of Bcl-2 expression.
Chemoresistance to concanamycin A1 in human oral squamous cell carcinoma is attenuated by an HDAC inhibitor partly via suppression of Bcl-2 expression.
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DOI：
10.1371/journal.pone.0080998
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sakai H
中科院分区：
文献类型：
--
作者：
Kiyoshima T;Yoshida H;Wada H;Nagata K;Fujiwara H;Kihara M;Hasegawa K;Someya H;Sakai H
V-ATP酶参与实体瘤（如口腔鳞状细胞癌（OSCC））周围/内部微环境的酸化。V-ATP酶被认为在几种恶性肿瘤中诱导肿瘤侵袭和多药耐药，并且它还通过诱导质子挤出到细胞外介质中来在酸性微环境下维持细胞内pH。然而，关于V-ATP酶抑制剂对OSCC的影响的信息很少。本研究探讨V-ATPase抑制剂康卡霉素A1（CMA）对口腔鳞癌细胞增殖和凋亡的影响。我们使用了四种OSCC细胞系，MISK 81 -5，SAS，HSC-4和SQUU-B。吖啶橙子染色显示低浓度CMA处理的OSCC细胞红色荧光均减少，表明低浓度CMA处理可阻止OSCC细胞内囊泡细胞器的酸化。CMA处理诱导MISK 81 -5、SAS和HSC-4细胞凋亡，但不诱导SQUU-B细胞凋亡。CMA处理的SQUU-B细胞中p-p38的表达没有改变，但它们的水平在其他细胞中增加。CMA处理的SQUU-B细胞中Bax/Bcl-2比值与CMA处理的其他细胞系相比显着降低。然而，当SQUU-B细胞与CMA和组蛋白去乙酰化酶抑制剂辛二酰苯胺异羟肟酸（SAHA）处理时，SQUU-B细胞变得更容易受到CMA诱导的凋亡。SAHA处理导致CMA处理的SQUU-B细胞中Bcl-2表达的显著降低，导致与仅用CMA处理的SQUU-B细胞中观察到的Bax/Bcl-2比率相比，Bax/Bcl-2比率显著增加。这些结果表明CMA可能对OSCC具有抗肿瘤作用。此外，CMA与其他药物（如SAHA）的组合可以帮助改善CMA的促凋亡作用，即使在CMA耐药的OSCC细胞中。
V-ATPase is involved in the acidification of the microenvironment around/in solid tumors, such as oral squamous cell carcinoma (OSCC). V-ATPase is thought to induce tumor invasion and multi-drug resistance in several malignant tumors, and it also contributes to maintaining the intracellular pH under an acidic microenvironment by inducing proton extrusion into the extracellular medium. However, there is little information regarding the effects of V-ATPase inhibitors on OSCCs. In this study, the effects of a V-ATPase inhibitor, concanamycin A1 (CMA), on the proliferation and apoptosis of OSCC were investigated in vitro. We used four OSCC cell lines, MISK81-5, SAS, HSC-4 and SQUU-B. Acridine orange staining revealed that the red fluorescence was reduced in all of the low concentration CMA-treated OSCC cells, indicating that the acidification of vesicular organelles in the OSCCs was prevented by the treatment with low-concentration of CMA. CMA treatment induced apoptosis in MISK81-5, SAS and HSC-4 cells, but not in SQUU-B cells. The p-p38 expression was not altered in CMA-treated SQUU-B cells, but their levels were increased in the other cells. The Bax/Bcl-2 ratio in CMA-treated SQUU-B cells was dramatically decreased in comparison with that in the other cell lines treated with CMA. However, when the SQUU-B cells were treated with CMA and a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), the SQUU-B cells became more susceptible to the CMA-induced apoptosis. SAHA treatment led to a significantly decrease in the Bcl-2 expression in CMA-treated SQUU-B cells, resulting in a dramatically increased Bax/Bcl-2 ratio in comparison with that observed in the SQUU-B cells treated with CMA alone. These findings suggest that CMA could have an anti-tumor effect on OSCCs. In addition, combination of CMA with other agents, such as SAHA, could help improve the pro-apoptotic effects of CMA even in CMA-resistant OSCC cells.
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影响因子：
3.7
作者：
Feng Z;Guo W;Zhang C;Xu Q;Zhang P;Sun J;Zhu H;Wang Z;Li J;Wang L;Wang B;Ren G;Ji T;Tu W;Yang X;Qiu W;Mao L;Zhang Z;Chen W
通讯作者：
Chen W
影响因子：
11.2
作者：
Ahmad, KA;Iskandar, KB;Pervaiz, S
通讯作者：
Pervaiz, S
影响因子：
11.2
作者：
Manero, F;Gautier, F;Juin, P
通讯作者：
Juin, P
影响因子：
4.8
作者：
Chidzonga, MM;Mahomva, L
通讯作者：
Mahomva, L
DOI：
10.1111/j.1349-7006.1994.tb02938.x
发表时间：
1994-12-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
MATSUO, K;ISHIBASHI, Y;SAKAI, H
通讯作者：
SAKAI, H