Wang Jing, Wu Qiong, Zhang Li-Hua, Zhao Yun-Xia, Wu Xin
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Department of Gynecology, Panjin Central Hospital, Panjin, 124010, China.
Tumour Biol. 2016 Mar;37(3):2879-90. doi: 10.1007/s13277-015-4087-6. Epub 2015 Sep 26.
Ras homologue gene family member A (RhoA) is involved in tumor mobility, invasion, and metastasis. We detected RhoA expression in vulvar squamous cell carcinoma (VSCC) tissue, measured RhoA expression in the VSCC cell phenotype, and measured the expression of the relevant molecules after RhoA small interfering RNA (siRNA) transfection in SW962 cells. RhoA has a higher expression level in VSCC than normal vulva skin tissue and was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and differentiation; besides, VSCC patients with lymph node metastasis had higher positive RhoA expression. RhoA messenger RNA and protein expression was significantly reduced in the RhoA siRNA transfectants as compared with the negative control (NC) and mock-transfected cells (p < 0.05). The RhoA siRNA transfectants lead to low growth, G1 arrest, high apoptosis, low migration and invasion (p < 0.05), and suppressed lamellipodia formation as compared to NC and mock-transfected cells. Besides, matrix metalloproteinase-2 (MMP2), MMP9, and cyclinA1 protein expression was downregulated, while that of Bax was upregulated in the RhoA siRNA transfectants (p < 0.05). SW962 cell proliferation rates were significantly lovastatin dose-dependent. Lovastatin caused G1 arrest, high apoptosis, low migration and invasion (p < 0.05), and suppression of lamellipodia formation. Similar to the RhoA siRNA transfectants, lovastatin treatment downregulated RhoA, MMP2, MMP9, and cyclinA1 protein expression, while upregulating that of Bax as compared to that of the NC (p < 0.05). Abnormal RhoA expression in vulvar carcinoma is involved in tumor proliferation and invasion and may be a treatment target. The RhoA inhibitor lovastatin alters VSCC cell migration and proliferation and may be effective for treating VSCC.
Ras同源基因家族成员A（RhoA）参与肿瘤的迁移、侵袭和转移。我们检测了外阴鳞状细胞癌（VSCC）组织中RhoA的表达，测定了VSCC细胞表型中RhoA的表达，并在SW962细胞中进行RhoA小干扰RNA（siRNA）转染后测定了相关分子的表达。RhoA在VSCC中的表达水平高于正常外阴皮肤组织，且与国际妇产科联盟（FIGO）分期及分化呈正相关；此外，发生淋巴结转移的VSCC患者RhoA阳性表达更高。与阴性对照（NC）和mock转染细胞相比，RhoA siRNA转染细胞中RhoA信使核糖核酸和蛋白表达显著降低（p < 0.05）。与NC和mock转染细胞相比，RhoA siRNA转染细胞导致生长缓慢、G1期阻滞、高凋亡率、低迁移和侵袭能力（p < 0.05），并抑制板状伪足形成。此外，RhoA siRNA转染细胞中基质金属蛋白酶-2（MMP2）、MMP9和细胞周期蛋白A1蛋白表达下调，而Bax表达上调（p < 0.05）。SW962细胞增殖率呈显著的洛伐他汀剂量依赖性。洛伐他汀导致G1期阻滞、高凋亡率、低迁移和侵袭能力（p < 0.05），并抑制板状伪足形成。与RhoA siRNA转染细胞相似，与NC相比，洛伐他汀处理下调了RhoA、MMP2、MMP9和细胞周期蛋白A1蛋白表达，同时上调了Bax表达（p < 0.05）。外阴癌中RhoA表达异常参与肿瘤增殖和侵袭，可能是一个治疗靶点。RhoA抑制剂洛伐他汀可改变VSCC细胞的迁移和增殖，可能对VSCC治疗有效。
