Wang Lingyan, Hou Jiayun, Wang Jianxin, Zhu Zhenghua, Zhang Wei, Zhang Xuemei, Shen Hui, Wang Xiangdong
Zhongshan Hospital Institute of Clinical Science, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Pharmaceutics, School of Pharmacy, Shanghai Medical College, Fudan University, Shanghai, China.
Clin Transl Med. 2020 Jun;10(2):e46. doi: 10.1002/ctm2.46. Epub 2020 Jun 5.
Actinidia chinensis Planch. root extract (acRoots) as one of Chinese traditional medications has been applied for antitumor therapy for decades, although the exact mechanisms have not been revealed. Our present study aimed to define the inhibitory specificity and pattern of acRoots in the lung cancer cell lines by comparing 40 types of cancer cell lines, select acRoots-associated inflammation target genes from transcriptional profiles of acRoots-sensitive and less-sensitive lung cancer cell lines, and validate the correlation of acRoots-associated inflammation target genes with prognosis of patients with lung cancer. We selected acRoots-sensitive (H1299) and less-sensitive lung cancer cells (H460) and found that the sensitivity was associated with the appearance of p53. The heat shock 70 kDa protein 6 (HSPA6) was defined as a critical factor in regulating cell sensitivity probably through the interaction with intra-HSPA family members, inter-HSP family members, and other families. The degree of cell sensitivity to acRoots increased in both sensitive and less-sensitive cells after deletion of HSPA6 genes. Thus, our data indicate that HSPA6 and HSPA6-dominated molecular network can be an alternative to modify cell sensitivity to drugs.
中华猕猴桃根提取物（acRoots）作为一种传统中药，已用于抗肿瘤治疗数十年，但其确切机制尚未明确。我们目前的研究旨在通过比较40种癌细胞系来确定acRoots对肺癌细胞系的抑制特异性和模式，从acRoots敏感和不敏感的肺癌细胞系转录谱中筛选与acRoots相关的炎症靶基因，并验证这些与acRoots相关的炎症靶基因与肺癌患者预后的相关性。我们选择了对acRoots敏感的（H1299）和不敏感的肺癌细胞（H460），发现敏感性与p53的出现有关。热休克70 kDa蛋白6（HSPA6）被确定为调节细胞敏感性的关键因子，可能是通过与HSPA家族内部成员、HSP家族成员之间以及与其他家族的相互作用来实现的。在缺失HSPA6基因后，敏感和不敏感细胞对acRoots的细胞敏感性程度均增加。因此，我们的数据表明，HSPA6和以HSPA6为主的分子网络可能是改变细胞对药物敏感性的一种替代方法。
