ABSTRACT
Breast cancer (Bca) remains the most common form of malignancy affecting females in China, leading to significant reductions in the mental and physical health of those with this condition. While spindle and kinetochore associated complex subunit 3 (SKA3) is known to be linked with cervical cancer progression, whether it is similarly associated with Bca progression remains unknown. Using shRNA, we specifically knocked down the expression of SKA3 in Bca cell lines and then assessed the resultant changes in cell proliferation using CCK-8 and colony formation assays. In addition, we used western blotting to quantify the expression levels of relevant proteins in these cells, and we assessed the interaction between SKA3 and polo-like kinase-1 (PLK-1) via co-immunoprecipitation.In this study, we observed elevated SKA3 expression in Bca tissues and cell lines. When we knocked down SKA3 expression in Bca cells, we were able to determine that it functions in an oncogenic manner so as to promote the growth and proliferation of these cells in vitro. From a mechanistic perspective, we were able to show that in Bca cells SKA functions at least in part via interacting with PLK-1 and preventing its degradation. In summary, we found that SKA3 is able to regulate PLK-1 degradation in Bca cells, thus controlling their growth and proliferation. These results highlight SKA3 as a potentially viable target for anti-cancer drug development aimed at combatting Bca.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Microtubule-Associated Proteins/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Female , Gene Knockdown Techniques , Humans , Microtubule-Associated Proteins/metabolism , Protein Stability , Proteolysis , Polo-Like Kinase 1ABSTRACT
Traditional Chinese medicine (TCM) Xiaoaiping shows a pharmacological activity in treatment of breast cancer. Although neoadjuvant chemotherapy has been more and more widely used in treatment of breast cancer in recent years, no report has been made about the clinical efficacy and mechanism of the combined application of neoadjuvant chemotherapy and Xiaoaiping in treatment of breast cancer. In this study, 66 patients with breast cancer were selected and divided into the control group and the treatment group evenly with the random number table method. All patients received TEC neoadjuvant chemotherapy. On that basis, the treatment group also received the adjuvant therapy of Xiaoaiping injection (60 mL, i. v. , qd). The short-term response rate and the follow-up survival rate of the two groups were observed and compared. Surgical specimens of the patient were collected to observe and compare their expressions of estrogen receptor ER-α36 in breast cancer tissues with the immunohistochemical method. According to the findings, the overall response rate of the treatment group was 78.79%, which was significantly higher than that of the control group (57.58% , χ2 = 5.48, P < 0.05). Compared with the control group, the treatment group showed significant increases in the disease-free survival (DFS) rate and the total survival rate at the 3rd year and 5th year (all P < 0.05) , and a notable reduction in ER-α36 expression in breast cancer tissues (P < 0.05). Based on the our results, Xiaoaiping can significantly enhance short-term ad long-term efficacies of neoadjuvant chemotherapy for breast cancer. Its mechanism may be correlated with the inhibition of ER-α 36 expression in breast cancer tissues.
Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Drugs, Chinese Herbal/administration & dosage , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Combined Modality Therapy , Drug Therapy, Combination , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Female , Humans , Middle Aged , Neoadjuvant Therapy , Treatment OutcomeABSTRACT
Epidemiological studies have been conducted to investigate the association between the FOXP3 promoter polymorphisms, rs3761549 and rs3761548, and the risk of cancer. However, the results from these studies have been controversial. In order to obtain a more precise conclusion of this association, the present meta-analysis was performed. The odds ratio (OR) and 95% confidence interval (95% CI) values were used to assess any correlations between the data. Overall, the rs3761549 (C>T) and rs3761548 (C>A) polymorphisms of the FOXP3 gene were not associated with the cancer risk in an Asian population. In the subgroup analyses based on cancer type, no significant associations were identified between these two polymorphisms and breast cancer. However, the results altered when the analyses were restricted to hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) (for rs3761549: TT+CT vs. CC OR, 0.52, 95% CI, 0.38-0.72; TC vs. CC OR, 0.25, 95% CI, 0.16-0.39; T vs. C OR, 0.76, 95% CI, 0.59-0.97. For rs3761548: AA vs. AC+CC OR, 3.20, 95% CI 1.76-5.81; AA+AC vs. CC OR, 2.56, 95% CI, 1.75-3.76; AA vs. CC OR, 4.41, 95% CI, 2.36-8.25; AC vs. CC OR, 2.15, 95% CI, 1.42-3.25; A vs. C OR, 2.32, 95% CI, 1.74-3.10). The present meta-analysis indicates that the FOXP3 rs3761549 (C>T) and rs3761548 (C>A) polymorphisms are not associated with the risk of breast cancer, but with the risk of HCC and NSCLC. Therefore, a study with a larger sample size is required to further evaluate this association.
