Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes the leading cause of cancer death worldwide. Ononin is an isoflavone glycoside known to have various pharmacological properties, including antioxidant and anti-inflammatory activities. In the present study, we aimed to investigate the efficacy of ononin on osteosarcoma cell migration, invasion, and the underlying mechanisms. The in vitro anti-tumorigenic and anti-migratory properties of ononin were determined by MTT, colony formation, invasion, and migration in MG-63 and U2OS osteosarcoma cell lines. The results were compared with the standard chemotherapeutic drug, doxorubicin (DOX), as a positive control. The dose-dependent manners of ononin treatment increased the expression of apoptosis and inhibition of cell proliferation through the EGFR-Erk1/2 signaling pathways. Additionally, ononin significantly inhibited the invasion and migration of human osteosarcoma cells. For consistency, we used the MG-63-xenograft mice model to confirm the in vivo anti-tumorigenic and anti-migratory efficacy of ononin by inhibiting the protein expressions of EGFR-Erk1/2 and MMP2/9. According to the histological study, ononin had no adverse effect on the liver and kidney. Overall, our findings suggested that ononin could be a potentially effective agent against the development and metastasis of osteosarcoma.

Lung cancer is a leading global cause of cancer-related death in both males and females. Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed cancer type that can be difficult to control with conventional chemotherapeutic and surgical approaches resulting in a poor prognosis. Paclitaxel (PTX) is a commonly used chemotherapeutic drug for NSCLC, which can cause tissue injury in healthy cells and affect the quality of life in patients with cancer. In order to treat NSCLC, alternative medications with minimal or no side effects are highly needed. Ononin is an isoflavone glycoside extracted from Astragali Radix (AR) that has various pharmacological activities. Therefore, this study investigated whether ononin inhibits NSCLC progression and promotes apoptosis synergistically with PTX both in vitro and in vivo. Antitumorigenic properties of ononin were determined by MTT assay, colony formation assay, migratory capacity, and apoptotic marker expression in A549 and HCC827 cells. The combination of ononin with PTX increased the expression of apoptotic markers and ROS generation and inhibited cell proliferation through the PI3K/Akt/mTOR signaling pathways. Furthermore, ononin prevented the translocation of NF-κB from cytosol to the nucleus. Also, we used the xenograft NSCLC mice model to confirm the in vivo antitumorigenic efficacies of ononin by reduction of CD34 and Ki67 expressions. Based on the histological analysis, the cotreatment of PTX and ononin reduced PTX-induced liver and kidney damage. Overall, our findings suggested that the therapeutic index of PTX-based chemotherapy could be improved by reducing toxicity with increasing antitumor capabilities when combined with ononin.

Danggui Buxue Tang (DBT) is a well-known Chinese herbal recipe often prescribed in clinical treatment for menopausal and cardiovascular symptoms. 5-Fluorouracil (5-FU) is a chemotherapy drug that treats several cancers; however, it causes severe adverse effects and multidrug resistance. Combining natural medications can reduce the side effects of 5-FU use. Hence, we aimed to determine the role of DBT in strengthening the anticancer capabilities of 5-FU in a cultured colorectal adenocarcinoma cell line (HT-29 cell) and xenograft nude mice. HT-29 cells cultured with DBT did not exhibit cytotoxicity. However, co-administration of DBT with 5-FU significantly increased apoptosis and the expression of apoptotic markers. The inhibition of proliferation induced by DBT and 5-FU was shown to be mediated by c-Jun N-terminal kinase signaling. In addition, the potentiation effect of 5-FU and DBT was demonstrated in reducing tumor size, expressions of Ki67 and CD34 in HT-29 xenograft mice. This finding suggests that DBT can work with 5-FU as a novel chemotherapeutic strategy for treating colon cancer. K E Y W O R D S 5-FU, co-administration, colorectal cancer, Danggui Buxue Tang 1 | INTRODUCTION Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with about 200 million new cases per year (Kuipers

As biodegradable orthopedic implant materials, magnesium alloys have been attracted enough attentions recently. However, too fast degradation in vivo, limited biocompatibilities, and insufficient antibacterial properties are three main challenges at present. In order to solve these problems, a multifunctional composite coating of Chi(Zn/BMP2)/HA was constructed on AZ31B magnesium alloy surface, successively by the alkali heating treatment, self-assembly of 16-phosphonyl-hexadecanoic acid, in situ immobilization of Chi(Zn/BMP2) (chitosan, zinc ions, and bone morphogenetic protein 2), and the deposition of HA (hydroxyapatite). The results of ATR-FTIR (attenuated total reflection Fourier transform infrared spectrum) spectra and elemental compositions confirmed that 16-phosphonyl-hexadecanoic acid, Chi(Zn/BMP2), and HA were successfully immobilized on the surface. Compared with Mg, Mg-OH, Mg-16, and Mg-Chi(Zn/BMP2), Mg-Chi(Zn/BMP2)/HA with the concave–convex structure surface significantly enhanced the hydrophilicity and corrosion resistance. On the other hand, Mg-Chi(Zn/BMP2)/HA coating also showed excellent biocompatibilities, which not only significantly promoted the osteoblast adhesion and proliferation, but also upregulated ALP and OCN expression of osteoblasts. Furthermore, due to the synergistic antibacterial effect of zinc ions and chitosan, Mg-Chi(Zn/BMP2)/HA showed a good antibacterial property against Escherichia coli (E. coli). Therefore, it can be said that the method used in this work has a good application prospect in improving the corrosion resistance, biocompatibility of magnesium alloys, and inhibiting infections against E. coli.

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