Glycyrrhizin Suppresses the Growth of Human NSCLC Cell Line HCC827 by Downregulating HMGB1 Level

Xiaojin Wu, Weitao Wang, Yuanyuan Chen, Xiangqun Liu, Jindong Wang, Xiaobin Qin, Dawei Yuan, Tao Yu, Guangxia Chen, Yanyan Mi, Jie Mou, Jinpeng Cui, Ankang Hu, Yunxiang E, Dongsheng Pei, Xiaojin Wu, Weitao Wang, Yuanyuan Chen, Xiangqun Liu, Jindong Wang, Xiaobin Qin, Dawei Yuan, Tao Yu, Guangxia Chen, Yanyan Mi, Jie Mou, Jinpeng Cui, Ankang Hu, Yunxiang E, Dongsheng Pei

Abstract

Lung cancer has very high mortality and glycyrrhizin was found to significantly inhibit the growth of lung cancer cells in vitro and tissues in mice. However, the detailed inhibitory role of glycyrrhizin in the growth of lung cancer is still unclear. In this study, we first found that glycyrrhizin inhibited the growth of lung tumor in PDX mice. And high level of HMGB1 promoted the migration and invasion of lung cancer cells, which was suppressed by glycyrrhizin. Moreover, glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which is the upstream regulator of HMGB1. Therefore, this study revealed a potential mechanism by which glycyrrhizin can inhibit the progression of lung cancer.

Figures

Figure 1
Figure 1
Morphology of lung cancer HCC827 cells in PDX mice.
Figure 2
Figure 2
Glycyrrhizin inhibits tumor growth in PDX mice. (a) indicates the morphology of lung cancer cells from the two groups by HE staining, bar = 100 μm. (b) indicates the size of tumors from the two groups. Tumors were excised from the two groups and the tumor sizes between the two groups were compared. (c) indicates the average weight of tumors in the two groups. The difference of tumor weights between the glycyrrhizin treatment and DMSO treatment (model) was significant. ∗∗p < 0.01, as compared to the model control by t-test.
Figure 3
Figure 3
The protein level of HMGB1 is suppressed by glycyrrhizin. (a) indicates the protein level of HMGB1 in lung tumor tissues from the two groups detected by IHC staining assay, bar = 100 μm. (b) indicates the quantitative results based on IHC staining assay. HMGB1-positive cells were counted in the two groups, respectively. ∗p < 0.05, as compared to the model control by t-test. (c) indicates the protein level of HMGB1 from the three groups by western blot. β-Actin was used as an internal control. p value was calculated by t-test between glycyrrhizin treatment and DMSO treatment (model). “NC” represents lung tissue from normal mice. ∗∗p < 0.01, as compared to the model control.
Figure 4
Figure 4
Glycyrrhizin inhibits the phosphorylation of Jak2 and Stat3. The phosphorylation level of Jak2 was detected by western blot in the three experimental groups, respectively. ∗∗p < 0.01, as compared to the model control (a). The phosphorylation level of Stat3 was detected by western blot in the three experimental groups, respectively. ∗∗p < 0.01, as compared to the model control (b). β-Actin was used as an internal control. p value was calculated by t-test between glycyrrhizin treatment and DMSO treatment (model). “NC” represents lung tissue from normal mice. Stars are showing p values between model and glycyrrhizin.

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Source: PubMed

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