A metalloproteinase of the disintegrin and metalloproteinases and the ThromboSpondin Motifs 6 as a novel marker for colon cancer: functional experiments.

Herein, we aimed to investigate the functions of ADAMTS6 in colon cancer and its potential mechanism. Based on the data acquired from TCGA database, we revealed that ADAMTS6 was highly expressed in colon cancer tissues, and high expression of ADAMTS6 predicted worse prognosis in patients with colon cancer. Moreover, qRT-PCR demonstrated that the levels of ADAMTS6 were higher in colon cancer cell lines (NCI-H508, Caco-2, CW-2 and HCT 116) than that in normal control cell line CCD-18Co. Functional experiments displayed that depletion of ADAMTS6 repressed NCI-H508 cell growth, invasion and migration whilst overexpression of ADAMTS6 facilitated Caco-2 cell growth, invasion and migration. Moreover, ADAMTS6 silencing enhanced the protein expression of E-cadherin and reduced the levels of N-cadherin, Vimentin and Snail in NCI-H508 cells, whereas ADAMTS6 overexpression showed the counter effects in Caco-2 cells. The protein levels of p-AKT and p-p65 were decreased by depletion of ADAMTS6 in NCI-H508 cells, while their levels were enhanced by overexpression of ADAMTS6 in Caco-2 cells. These consequences indicated that the accelerating effect of ADAMTS6 on colon cancer cell growth, migration and invasion might be achieved by modulating EMT and AKT/NF-κB signaling pathway, offering important foundations for colon cancer treatment.

[Dose-response patterns of Radix Glycyrrhizae in Shanghan Lun].

In order to explore the dose-response patterns of Gancao (Radix Glycyrrhizae) in Shanghan Lun (Treatise on Febrile Diseases), all prescriptions containing Gancao in Shanghan Lun were analyzed by frequency and hierarchical clustering analysis. The doses of Gancao used in Shanghan Lun ranged from six zhu (Chinese unit, and one zhu is equal to 0.65 g) to four liang (Chinese unit, and one liang is equal to 15.625 g). Doses of one, two, three or four liang were commonly used. One liang Gancao as juvantia was usually matched with Mahuang (Herba Ephedrae), Xingren (Semen Armeniacae) and Guizhi (Ramulus Cinnamomi) for restricting the excessive diaphoresis of Mahuang. Two liang Gancao was often matched with some couple drugs, such as Guizhi and Shaoyao (Radix Paeoniae), Shigao (Gypsum Fibrosum) and Zhimu (Rhizoma Anemarrhenae), Fuzi (Radix Aconiti Lateralis) and Ganjiang (Rhizoma Zingiberis), for warming yang to supplement qi, nourishing yin, detoxifying Fuzi, and preventing qi impairment from heat evil. Three liang Gancao was mainly matched with Banxia (Rhizoma Pinelliae) or Renshen (Radix Ginseng) for treating middle energizer emesis. Four liang Gancao was matched with Ganjiang or tonifying herbs for invigorating vital qi and relieving spasm in deficiency syndromes with contraction, palpitation or diarrhea. Gancao is used for treating many syndromes in Shanghan Lun. It is frequently used to treat excess or heat syndromes with one or two liang in a dose and deficiency or cold syndromes with three or four liang in a dose.