Zhang Qiuyan, Gao Lei, Huang Songli, Liang Yuxi, Hu Jingyan, Zhang Yuan, Wei Shengli, Hu Xiuhua
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2022 Jun 1;13:880215. doi: 10.3389/fphar.2022.880215. eCollection 2022.
Malignant melanoma has high morbidity and mortality and limited treatment options. Traditional Chinese medicine has great potential in the clinical therapy of cancer, and the theory of compatibility is one core content of Chinese medical theory. and are clinically effective for the treatment of various cancers. We verified the effects of AMD, RTD, and their "cocktail" on melanoma model and and the mechanism of its effect on the Akt-related signaling pathway by network pharmacology, MTT, flow cytometry, LDH, SOD, MDA assay, and Western blot. The network pharmacology analysis indicated that the PI3K-Akt pathway plays a crucial role in the treatment of malignant melanoma with these two herbs. In addition, AMD, RTD, and their "cocktail" could inhibit the proliferation of A375 cells by reducing the survival rate in a concentration-dependent manner and by regulating the cell cycle, and the compatibility of two herbs also could inhibit melanoma growth. They could, respectively, induce apoptosis and inhibit migration by affecting the expression of Bcl-2, Bax, p53, snail, E-cadherin, and N-cadherin. Furthermore, LDH activity was decreased, while SOD increased and MDA reduced. The factors of the Akt-related signaling pathway, Akt and p-Akt, were decreased. This study showed that AMD, RTD, and their "cocktail" could regulate cell proliferation, apoptosis, and metastasis in A375 cells through the suppression of the Akt-related signaling pathway, and the "cocktail" groups had detoxification and additive effects. The best compatibility of the two herbs also can inhibit tumor growth and metastasis
恶性黑色素瘤发病率和死亡率高,治疗选择有限。中医在癌症临床治疗中具有巨大潜力,配伍理论是中医理论的核心内容之一。[具体药物名称1]和[具体药物名称2]在临床上对多种癌症的治疗有效。我们通过网络药理学、MTT法、流式细胞术、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)检测以及蛋白质免疫印迹法,验证了[具体药物名称1]、[具体药物名称2]及其“合剂”对黑色素瘤模型[模型名称1]和[模型名称2]的作用及其对Akt相关信号通路的作用机制。网络药理学分析表明,PI3K - Akt通路在这两种草药治疗恶性黑色素瘤中起关键作用。此外,[具体药物名称1]、[具体药物名称2]及其“合剂”可通过浓度依赖性降低存活率和调节细胞周期来抑制A375细胞增殖,两种草药的配伍也可抑制黑色素瘤生长。它们可分别通过影响Bcl - 2、Bax、p53、蜗牛蛋白(snail)、E - 钙黏蛋白(E - cadherin)和N - 钙黏蛋白(N - cadherin)的表达诱导细胞凋亡并抑制细胞迁移。此外,LDH活性降低,而SOD升高,MDA降低。Akt相关信号通路的因子Akt和p - Akt减少。本研究表明,[具体药物名称1]、[具体药物名称2]及其“合剂”可通过抑制Akt相关信号通路调节A375细胞的增殖、凋亡和转移,“合剂”组具有解毒和相加作用。两种草药的最佳配伍还可抑制肿瘤生长和转移