The Effect of Chrysin Loaded PLGA-PEG on Metalloproteinase Gene Expression in Mouse 4T1 Tumor Model

Abstract

Despite the advances in medicine, cancer remains as one of the leading causes of the death worldwide. Through our previous study, the Chrysin loaded PGLA/PEG has been synthesized, and its physico-chemical properties were characterized. The aim of the present study was to evaluate the Chrysin loaded PGLA/PEG nanoparticle therapeutic effects on TIMP-1, TIMP-2, MMP-2, MMP-9 and PI3k expression in Mouse 4T1 breast tumor model.30 mice were enrolled in the current study, and the mice were randomly divided into 3 groups: untreated (n=10), Chrysin treatment (n=10) and Chrysin-loaded PLGA/PEG-based treatment (n=10). 104T1 mammary carcinoma cells subcutaneously inoculated in the flank on mice orthotopically. After the treatments, the primary tumors were isolated from the Mice under anesthesia. For RNA extraction, the isolated tissues were frozen in -70°C. RNA extraction was performed by using RNA extraction kit. The expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 were measured by the real time PCR.The study results showed the expression of TIMP-1 and TIMP-2 in Chrysin-loaded PLGA/PEG treatment groups was higher than Chrysin receiving one. Also, the results showed that the MMP-9 and MMP-2 expressions were reduced after Chrysin loaded PLGA/PEG treatment. The reduction of the mentioned genes was greater in Chrysin-loaded PLGA/PEG treatment group in comparison with Chrysin receiving group.According to our present study, expression of the mentioned genes after treatments, Chrysin; especially, Chrysin-loaded PLGA/PEG could be proposed as a new component in the cancer therapy for reducing the progression and metastasis.

Effects of nano-encapsulated curcumin-chrysin on telomerase, MMPs and TIMPs gene expression in mouse B16F10 melanoma tumour model

“…In our previous study, Chrand Chr-loaded PLGA-PEG NPs decreased the expression of MMP-9 and MMP-2 in mouse 4T1 breast tumour model. According to the results of this study, the reduction of the mentioned genes was greater in Chr-loaded PLGA/PEG treatment group in comparison with Chr receiving group [51]. These findings are in line with the results obtained in this study that showed the level of MMP-9 and MMP-2 genes expression were significantly decreased after treatment with Cur and Chr in all groups in the C57B16 mouse model of melanoma.…”

“…We did not find any study evaluating the effect of Chr on TIMPs expression in melanoma cancer. However, in our previous study, we demonstrated that the expression of TIMP1 and TIMP2 were increased after treatment with pure and nano-encapsulated Chr in PLGA-PEG in mouse 4T1 breast tumour model and the observed rise in nano-encapsulated Chr was greater [51]. In this study, we found that treatment with Cur and Chr in the C57 B16 mouse model of melanoma, significantly increased the level of TIMP-1 and TIMP-2 genes expression, compared to the control.…”

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

“…Chrysin- and curcumin-loaded nanoparticles significantly promote the expression of TIMP-1 and TIMP-2 to exert a reduction in melanoma invasion [ 310 ]. Taking everything into account, studies agree with the fact that nanoparticles can enhance the anti-tumor activity of chrysin against cancer cells [ 62 , 312 , 313 , 314 , 315 , 316 ]. Nanoparticles can provide a platform for the co-delivery of chrysin and other anti-tumor agents that is important in promoting its inhibitory effect against cancer cells ( Figure 4 ) ( Table 3 ).…”

Synergistic Effect of Free and Nano-encapsulated Chrysin-Curcumin on Inhibition of hTERT Gene Expression in SW480 Colorectal Cancer Cell Line

“…Chrysin (5, 7-dihydroxyflvone) is a member of flavones with a wide range of biological effects such as antioxidative and anti-inflammatory properties [15,16]. Also, recent studies have shown that chrysin can be a good candidate for the treatment of various cancers due to molecular chemopreventive effects, biological properties, good safety, low toxicity and anti-cancer property [16][17][18][19][20]. Also, curcumin as a polyphenol compound have property of antioxidant, anti-inflammatory, reduction of blood cholesterol, anti-neoplastic and anti-cancer [21][22][23].…”