| Breast cancer has surpassed lung cancer to become the most common cancer in the world in 2020.There are approximately 2 million new breast cancer patients each year,accounting for about 11.7% of all new cancer patients.Hormone receptor-positive breast cancer is the subtype with the highest incidence,accounting for about 70% of all breast cancer patients.Previous studies have shown that the occurrence and development of breast cancer are closely related to the tumor cell microenvironment and the role of tumor cells themselves.Among them,the regulation of the extracellular matrix protein Tenascin-C（TNC）and its cell membrane receptor integrin on tumor cells has been paid more and more attention.At the same time,the tumor suppressor genes PTEN and PI3K/AKT signaling pathway,which are closely related to the occurrence and development of breast cancer in tumor cells,have also been studied in depth.Antlers,a famous Chinese medicinal material,are mainly used to treat various inflammatory reactions and mammary gland hyperplasia and other diseases.Hard antler extract（HAE）has important functions such as nourishing yin and yang,strengthening muscles and bones,anti-inflammatory and anti-tumor.And our previous study showed that HAE can inhibit the proliferation and invasion of triple-negative and Her-2 breast cancers.This study aimed to investigate the antitumor effect of antler disc extract on hormone receptor-positive breast cancer and to explore its underlying mechanism.Method:（1）7,12-Dimethylphenanthene（DMBA）gavage induced breast carcinogenesis and established a hormone receptor-positive breast cancer model.Hard antler extracts were used as the observation group,tamoxifen as the positive control,sodium carboxymethyl cellulose（CMC）solvent as the negative control and administration was gavage.Rat body weight and tumor size were measured three times a week,and the tumor volume was calculated（2）Pathological tissue sections were examined to confirm the tumor nature,hormone receptor status,and liver and kidney tissue status.（3）Detecting the effect of HAE on the expression of extracellular matrix and cell membrane receptors in tumor tissues by immunohistochemistry and immunofluorescence staining.（4）Detecting the effect of antlers on the number of stem cells in tumor tissues by immunofluorescence and immunohistochemical staining.（5）Detecting the effect of antlers on the changes of intracellular signal pathways in tumor tissues by western blot.（6）Transwell experiment was used to verify the effect of antlers on the transfer and invasion of hormone receptor-positive cells MCF-7.Result:（1）Rats were successfully induced to form tumors by DMBA and confirmed to be hormone-receptor-positive breast cancer.HAE delayed the occurrence of hormone-receptorpositive breast cancer in rats and inhibited the growth of tumors.Tamoxifen completely effectively prevented the occurrence of hormone receptor-positive breast cancer but reduced the weight of rats.（2）Compared with the negative control group,the expression of extracellular matrix Tenascin-C and cell membrane receptor IntegrinαVβ1 decreased in the observation group.（3）Compared with the negative control group,the expression of tumor stem cell markers CD24,CD44 and ALDH1 decreased in the observation group.（4）Compared with the negative control group,the expression of tumor suppressor gene PTEN was increased,and the phosphorylation expression of AKT was decreased in the observation group.（5）HAE inhibited the transfer and invasion ability of hormone receptor-positive cells MCF-7.Conclusion:HAE effectively prevents the occurrence of hormone receptor-positive breast cancer and tumor growth,and the mechanism may be related to Tenascin-C/IntegrinαVβ1 and PI3K/AKT signaling pathways. |
