br and MMP were dramatically decreased after treatments with CNC
and MMP-9 were dramatically decreased after treatments with CNC, in-dicating that CNC could suppress cell metastasis by inhibiting activities of MMPs. The relatively quantitative levels of MMP-2 and MMP-9 were shown in Fig. 7B. The expressions of apoptosis related proteins were subsequently detected, such as Bcl-2 and Bax. One of the principal roles of Bcl-2 family is the regulation of the initiation of apoptosis by the mitochondrial pathway . As shown in Fig. 7A and B, CNC could suppress the expression of Bcl-2 and increase the expression of Bax in tumor cells, and the effects were associated with the concentration. The results were consistent with those in immunohistochemical analy-sis. Results above indicated that CNC could inhibit metastasis and induce apoptosis of SGC-7901 FK506 through regulating the expressions of MMP-2, MMP-9, Bcl-2 and Bax, further illustrating the underlying mechanisms of the higher antitumor effects performed by CNC.
In this study, norcantharidin-conjugated carboxymethyl chitosan (CNC) was designed for the delivery of NCTD, aiming to enhance its an-titumor efficiency in clinical application. Our results suggested that the conjugates could significantly inhibit cell proliferation and induce the apoptosis of SGC-7901 cells. Besides, the metastasis and tube formation of HUVECs were obviously inhibited after incubation with CNC. CNC possessed higher antitumor capacity than that of free NCTD in BALB/c nude tumor-bearing mice with a tumor inhibition rate of 59.57%. Inves-tigation for the underlying mechanisms revealed that the enhanced an-titumor effects might be mediated by the increasing expression of TNF-
α and the reduced expressions of CD34, VEGF, MMP-2 and MMP-9. Fur-thermore, western blot assay and immunohistochemistry analysis dem-onstrated that CNC induced cell apoptosis through down-regulating the expression of Bcl-2 and increasing the expressions of Bax and Caspase-3. Overall, our results suggested the potential applicability of CNC as novel polymer therapeutics for gastrointestinal cancer treatment.
 Y. Wang, M. Huang, R. Sun, L. Pan, Extraction, characterization of a ginseng fruits polysaccharide and its immune modulating activities in rats with Lewis lung carci-noma, Carbohydr. Polym. 127 (2015) 215–221.
 R. Budiraharjo, K.G. Neoh, E.T. Kang, Hydroxyapatite-coated carboxymethyl chitosan scaffolds for promoting osteoblast and stem cell differentiation, J. Colloid Interface Sci. 366 (1) (2012) 224–232.
 A. Khanjari, I.K. Karabagias, M.G. Kontominas, Combined effect of N,O-carboxymethyl chitosan and oregano essential oil to extend shelf life and control listeria monocytogenes in raw chicken meat fillets, LWT-Food Sci. Technol. 53 (1) (2013) 94–99.
 S. Jiang, M. Li, Y. Hu, Z. Zhang, H. Lv, Multifunctional self-assembled micelles of galactosamine-hyaluronic acid-vitamin E succinate for targeting delivery of norcantharidin to hepatic carcinoma, Carbohydr. Polym. 197 (2018) 194–203.
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Pathology - Research and Practice
journal homepage: www.elsevier.com/locate/prp
Apatinib enhanced anti-tumor activity of cisplatin on triple-negative breast T cancer through inhibition of VEGFR-2
Zhenyuan Gao, Mohan Shi, Yaping Wang, Juan Chen, Yimei Ou
Department of Medical Oncology, The First Aﬃliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, PR China
Triple-Negative breast cancer
Background: Triple-negative breast cancer (TNBC) was known as a fast-growing and an aggressive tumor. Cisplatin is the eﬀective cytotoxic drug used for the treatment of TNBC. In addition, apatinib, a VEGFR2 in-hibitor, exhibits antitumor activity in patients with TNBC. However, the eﬀects of combination of apatinib with cisplatin on TNBC remain unclear. Thus, this study aimed to investigate the eﬀects of apatinib in combination with cisplatin on MDA-MB-231 cells.