Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Abstract

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

“…International Agency for Research on Cancer has considered nickel as one of the carcinogenic agents [ 123 , 124 , 125 ]. Exposing to nickel-containing compounds is correlated with the risk of lung cancer development [ 126 , 127 ].…”

Kangai Injection Combined with Platinum-based Chemotherapy for the Treatment of Stage III/IV Non-Small Cell Lung Cancer: A Meta-analysis and Systematic Review of 35 Randomized Controlled Trials

“…Its China Food and Drug Administration number is Z20026868. Active compounds of KAI include astragalus polysaccharides, astragalosides, ginsenosides, ginseng polysaccharide and oxymatfine [12], and various studies have shown that KAI possesses multiply pharmacological effects: (1)inducing tumor cell apoptosis [13,14]; (2)inhibiting tumor cell proliferation, invasion and metastasis [15,16]; (3)increasing the sensitivity of chemotherapy drugs and reducing adverse events caused by chemotherapy [17][18][19]; (4)improving the body's immune function [20][21][22]. In the clinic, Fan et al found that KAI has obtained good curative effect, could ultimately prolong the survival and improve the quality of life, and mainly used in the treatment of multi-cancers, including liver, lung, colorectal cancer, etc.…”

Clinical outcomes of chemotherapy in patients with undifferentiated carcinoma of the pancreas: a retrospective multicenter cohort study

“…On the other hand, the mechanism of the effect of paclitaxel on UC is unclear. Paclitaxel, including nabpaclitaxel, is a widely used chemotherapy drug for various cancers, including PC [26][27][28]. However, many studies have reported that the EMT is associated with acquired resistance to chemotherapy drugs [29][30][31], including paclitaxel [32].…”