Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Animal Laboratory Center, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Mol Carcinog. 2020 Jun;59(6):575-589. doi: 10.1002/mc.23182. Epub 2020 Mar 18.
Dihydromethysticin (DHM), a natural compound derived from Kava, has been reported to be effective against mental disorders and some malignant tumors. However, little is known about the inhibitory effect of DHM on colorectal cancer (CRC). First, we examined the impact of DHM on human colon cancer cell lines, which demonstrated that DHM inhibits proliferation, migration, and invasion and promotes apoptosis and cell cycle arrest in colon cancer cells in vitro. Using small hairpin RNA, we inhibited nucleotide-oligomerization domain-like receptor subfamily C3 (NLRC3)/phosphoinositide 3-kinase (PI3K) pathway to elucidate the partial signaling of DHM-mediated tumor suppression. Additionally, using an ectopic human CRC model, we verified whether DHM inhibits tumor growth and angiogenesis via the NLRC3/PI3K pathway in vivo. Overall, DHM showed an inhibitory effect on CRC by altering cell proliferation, migration, invasion, apoptosis, cell cycle, and angiogenesis, possibly via the NLRC3/PI3K pathway. Thus, DHM may be a promising candidate for CRC therapy.
二氢麦角隐亭（DHM），一种源自卡瓦的天然化合物，据报道对精神障碍和一些恶性肿瘤有效。然而，关于 DHM 对结直肠癌（CRC）的抑制作用知之甚少。首先，我们研究了 DHM 对人结肠癌细胞系的影响，结果表明 DHM 可抑制体外结肠癌细胞的增殖、迁移和侵袭，并促进细胞凋亡和细胞周期停滞。使用短发夹 RNA，我们抑制核苷酸寡聚化结构域样受体亚家族 C3（NLRC3）/磷酸肌醇 3-激酶（PI3K）通路，以阐明 DHM 介导的肿瘤抑制的部分信号。此外，我们使用异位人 CRC 模型在体内验证了 DHM 是否通过 NLRC3/PI3K 通路抑制肿瘤生长和血管生成。总的来说，DHM 通过改变细胞增殖、迁移、侵袭、凋亡、细胞周期和血管生成来抑制 CRC，可能通过 NLRC3/PI3K 通路。因此，DHM 可能是 CRC 治疗的有前途的候选药物。
