α- 倒捻子素对MCF-7 乳腺癌增殖、生长和侵袭的影响及其作用机制

Effect of α-mangostin on proliferation, growth and invasion of MCF-7 breast cancer and its mechanisms

摘要:

目的 探讨α- 倒捻子素对MCF-7 乳腺癌增殖、生长和侵袭的影响及其作用机制。方法 采用细胞增殖实验（MTS 法）研究α- 倒捻子素对MCF-7 乳腺癌细胞体外增殖的影响；采用裸鼠皮下移植瘤模型研究α- 倒捻子素对MCF-7 乳腺癌体内生长的影响；采用Transwell 实验研究α- 倒捻子素对MCF-7乳腺癌细胞侵袭的影响；采用免疫组织化学法研究α- 倒捻子素对MCF-7 乳腺癌皮下移植瘤组织中翻译控制肿瘤蛋白（TCTP）、基质金属蛋白酶MMP-2 及MMP-9 蛋白表达的情况；采用Western blot 研究α- 倒捻子素对MCF-7 细胞中Erk、P38、MMP-2 及MMP-9 蛋白表达的影响。结果 体外增殖实验结果显示，α- 倒捻子素能够抑制MCF-7 乳腺癌细胞的增殖，且具有浓度和时间依赖性；α- 倒捻子素能够剂量依赖性地抑制MCF-7 乳腺癌的体内生长；α- 倒捻子素能够抑制MCF-7 乳腺癌细胞的侵袭；免疫组织化学结果显示，α- 倒捻子素能够下调TCTP、MMP-2 及MMP-9 的蛋白表达；Western blot 结果显示，α- 倒捻子素能够抑制调控肿瘤细胞增殖及侵袭相关蛋白的表达，如磷酸化的Erk、磷酸化的P38、MMP-2 及MMP-9。结论 α- 倒捻子素能够抑制MCF-7 乳腺癌增殖、生长及侵袭，其机制可能与抑制调控肿瘤细胞增殖及侵袭相关蛋白的表达有关。

Abstract:

Objective To explore the effect of α-mangostin on proliferation, growth, and invasion of MCF-7 breast cancer and its mechanisms. Methods MTS was used to study the effect of α-mangostin on in vitro proliferation of MCF-7 breast cancer cells. MCF-7 breast cancer xenograft model was used to examine the effect of α-mangostin on in vivo growth of the tumor. The effect of α-mangostin on invasion ability of MCF-7 breast cancer cells was examined by Transwell experiment. Immunohistochemistry was used to study the effect of α-mangostin on the expressions of translationally-controlled tumor protein (TCTP), matrix metalloproteinase-2 (MMP-2) and MMP-9 in MCF-7 subcutaneous transplantation tumor tissue. Western blot was used to detect the expressions of Erk, p38,MMP-2 and MMP-9 proteins. Results The proliferation of MCF-7 breast cancer cells was significant inhibited by α-mangostin in vitro compared to the control group. α-mangostin significantly inhibited the growth of MCF-7 breast cancer subcutaneous transplantation tumor in vivo compared to the control group. The invasion ability of MCF-7 breast cancer cells was significantly inhibited by α-mangostin. The expressions of TCTP, MMP-2 and MMP-9 were significantly inhibited by α-mangostin as shown in immunohistochemistry. The results of Western blot showed that α-mangostin inhibited the expressions of MMP-2, MMP-9, p-Erk and p-p38. Conclusions α-mangostin has anti-proliferation, anti-growth and anti-invasion effect on MCF-7 breast cancer, and such effect can attribute to its inhibition of growth and invasion-related proteins in MCF-7 breast cancer.