FRAS1 knockdown reduces A549 cells migration and invasion through downregulation of FAK signaling.

Distal metastasis is the major cause of death for the vast majority of lung cancer patients. Many extracellular matrix (ECM)-related molecules are proposed to be associated with the migration and invasion of cancer cells. FRAS1 encodes an ECM protein, however, little is known about its function on tumorigenesis and metastasis of lung cancer. In this work, FRAS1 was silenced by shRNA in non-small cell lung cancer (NSCLC) A549 cell line. The capacities of A549 cells to migrate and invade were decreased markedly after FRAS1 knockdown. The shRNA knockdown of FRAS1 was found to be specific and had no effect on A549 cells proliferation. Western blot experiments demonstrated that FRAS1 knockdown inhibited FAK signaling but not Src signaling. Overall, we found that FRAS1 knockdown reduces A549 cells migration and invasion ability through downregulation of FAK signaling.

[Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway].

OBJECTIVE: To study the effects of deguelin on proliferation and apoptosis of human breast cancer cell line MCF-7 and on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: After treatment with 0, 1, 5, 10, 15 and 20 µmol/L of deguelin for 6, 24, 48 and 72 hours, the proliferation inhibition rate of MCF-7 cells was measured by cell counting kit-8 assay. Apoptosis rate of MCF-7 cells was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry and the apoptotic morphology was observed under a transmission electron microscope. After treatment with 0, 1 and 5 µmol/L of deguelin for 6 hours, 5 proteins involved in the PI3K/Akt signaling pathway were examined by Western blot analysis. RESULTS: Deguelin at doses of 5, 10, 15 and 20 µmol/L inhibited the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours. There was a significant difference in each group compared with the control group (P<0.01). The inhibitory effect was more marked with increasing concentration and duration of treatment. There were statistical differences (P<0.05) among 5, 10, 15 and 20 µmol/L groups. However, 1 µmol/L of deguelin had no obvious effects on the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours, showing no significant difference compared with control group (P>0.05). Deguelin at doses of 5, 10, 15 and 20 µmol/L induced apoptosis of MCF-7 cells at 6 hours. There were significant differences (P<0.01) in the early and late apoptosis rate between the treated groups and the control group. The typical apoptotic MCF-7 cells were observed under the transmission electron microscopy. However, 1 µmol/L of deguelin had no apparent effect in inducing apoptosis of MCF-7 cells at 6 hours. After treatment with 5 µmol/L of deguelin for 6 hours the expression of phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (Ser380), phosphorylated 3-phosphoinositide-dependent protein kinase 1 (PDK1) (Ser241), phosphorylated Akt (Thr308) and phosphorylated glycogen synthase kinase-3ß (GSK-3ß) (Ser9) proteins were significantly reduced in MCF-7 cells, while there was no significant change in the expression of total Akt protein. However, after treatment with 1 µmol/L of deguelin for 6 hours, there was no apparent change in the expression of these 5 proteins. CONCLUSION: Deguelin can inhibit the phosphorylation of GSK-3ß (Ser9) via inhibition of the phosphorylation of PTEN (Ser380) and PDK1 (Ser241) pathway, thus inducing apoptosis and inhibiting proliferation of MCF-7 cells.

[A meta-analysis of the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer].

OBJECTIVE: To evaluate whether there is a difference in the curative effect of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer (NSCLC). METHODS: The databases PudMed, CENTRAL, and Chinese biomedical database were retrieved by using the key words "non-small cell lung cancer" or "carcinoma, non-small cell lung" so as to search the materials about the randomized controlled clinical trials that had compared the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance NSCLC. A meta-analysis was conducted. RESULTS: Eighteen documents about randomized controlled clinical trials, including 6478 patients, from the retrieved 3531 documents accorded to the demand of enrollment. The overall response rates of the carboplatin-based and cisplatin-based chemotherapeutic groups were both 27% (RR = 0.93, 95% CI = 0.86 approximately 1.01, P = 0.10). Neither funnel plot nor rank correlation test regarding response rate indicated the existence of publication bias (chi(2) = 18.63, P = 0.63). The 0ne-year survival rate of the carboplatin-based regimen group was 36%, not significantly different from that of the cisplatin-based regimen group (35%, RR = 1.04, 95% CI = 0.93 - 1.17, P = 0.5). Sensitive analysis confirmed the non-existence of differences in the overall response rate and one-year survival rate between these 2 groups. CONCLUSION: The curative effects of the carboplatin-based and cisplatin-based chemotherapeutic regimens are similar. The choice of carboplatin or cisplatin depends on the toxicity of the drugs and the patients' tolerance.