ABSTRACT
ObjectiveTo investigate the effects and molecular mechanism of ursolic acid on the proliferation and apoptosis of colorectal cancer cells. MethodThe proliferation inhibition rate of human colorectal cancer RKO cells treated with different concentrations of ursolic acid （0， 5， 10， 15， 20， 25， 30 μmol·L-1） was detected by cell counting kit-8 （CCK-8）， and the half maximal inhibitory concentration （IC50） at 24 h and 48 h was calculated. According to the IC50 of RKO cells treated with ursolic acid for 24 h， two concentrations were selected for subsequent experiments. The colony formation assay was used to detect the proliferation ability of the cells and flow cytometry was used to detect the apoptosis rate and cell cycle arrest after treatment of RKO cells with ursolic acid. After treatment of RKO cells with ursolic acid for 24 hours， the expression of B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax） in RKO cells， Bcl-2 in Raji cells， PMA responsive gene in T lymphocyte （Noxa）， cyclin-dependent kinase inhibitor 1A （p21）， cyclin-dependent kinase inhibitor 1B （p27）， cyclin-dependent kinase 4 （CDK4）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， forkhead transcription factor O3a （FoxO3a）， and phosphorylated FoxO3a （p-FoxO3a） was determined by Western blot. ResultCompared with the blank group， the ursolic acid groups could inhibit the viability of RKO cells （P<0.05， P<0.01）， and the colony formation rates of RKO cells in the ursolic acid groups were reduced （P<0.05， P<0.01） in a concentration-dependent manner. The cells in the ursolic acid group （20 μmol·L-1） experienced cell cycle arrest， which increased in the early stage of synthesis， ie， the G0/G1 phase （P<0.05） as compared with the results in the blank group. Compared with the blank group， the ursolic acid groups （15 and 20 μmol·L-1） showed increased protein expression of p21 and p27， decreased expression of CDK4 protein （P<0.05， P<0.01）， and increased apoptosis rate， and the ursolic acid group （20 μmol·L-1） showed increased protein expression of Bax and Noxa and decreased expression of Bcl-2 （P<0.05， P<0.01）. In terms of mechanism， compared with the blank group， the ursolic acid group （20 μmol·L-1） down-regulated the expression of p-Akt protein and up-regulated the expression of p-FoxO3a （P<0.05， P<0.01）， and there was no significant change in the total protein of Akt and FoxO3a. ConclusionUrsolic acid can effectively inhibit the proliferation of colorectal cancer RKO cells and promote cell apoptosis， which may be related to the Akt/FoxO pathway.
ABSTRACT
Background and purpose:At present,the treatment of metastatic breast cancer has remained diff icult for patients who have failed after the use of anthracycline and taxane,so the treatment options for those with advanced metastatic breast cancer are very limited.Therefore,pemetrexed combined with cisplatin in the treatment of anthracycline and taxane failed advanced metastatic breast cancer patients,its effi cacy and adverse reactions were studied.Methods:10 patients with advanced metastatic breast cancer patients received pemetrexed and cisplatin chemotherapy,pemetrexed 500mg/m2 intravenous infusion,cisplatin 75mg/m2 intravenous drip,repeated every 3 weeks.Evaluation of response and adverse reactions were practiced every 2 cycles.Results:10 patients were evaluable,CR 1 patient,PR 4 patients,SD 2 patients,PD 3 patients.With a median follow-up of 6 months(4-18 months),8 patients survived and 2 patients died.The median time to progression was 4 months(3-14 months),the median survival time was 8 months(4-18 months).The most common adverse reaction was fatigue,white blood cells decrease and the digestive tract reactions,followed by oral ulcers.Conclusion:Pemetrexed combined with cisplatin in the treatment of anthracycline and taxane treatment failed patients with advanced metastatic breast cancer could improve survival,adverse reactions could be tolerated.
ABSTRACT
Background and purpose:Advanced and metastatic colorectal cancer is the second leading cause of cancer death. In the past ,the standard treatment for patients with advanced CRC was fluorouracil(5-FU) biochemically modulated by leucovorin(LV), which demonstrated a response rate of about 23% .In 1990s, a number of new treatment options have been available. In particular, one new cytotoxic agent ,irinotecan (CPT-11), which is a specific inhibitor of topoisomerase I, have been proven to have efficacy in the tretment of CRC .Furthermore, several first-line phase Ⅲ trials show a significant improvement in result with the addition of CPT-11 to FU-LV combination therapy (FOLFIRI).We observed the survival situation, efficacy and safety of irinotecan plus 5-FU/LV after first-line chemotherapy failure for Chinese patients with advanced or/and metastatic colorectal cancer. Methods:Twenty-four patients with metastatic colorectal cancer whose disease had progressed after treatment with first-line oxaliplatin or other chemotherapeutics were included to receive biweekly FOLFIRI regimen (irinotecan 180mg/m~ 2 on day 1,with LV 200mg/m~ 2 adiministrated as a 2-hour infusion before 5-FU 400mg/m~ 2 administrated as an intravenous bolus injection and FU⒉4g/m~ 2 as 46-hour infusion immediately after 5-FU bolus ).All the patients were planned to receive at least 6 cycles of chemotherapy .They were assessed on the basis of WHO evaluation standard of objective therapeutic effect for solid tumor.Results:24 patients were assessable to observe the efficacy and safety. No case was CR.5 case were PR, response rate was 20% (5/24). 17 case were SD , rate was 70% (17/24). 2 case were PD, rate was 8%(2/24). Median time to progression (TTP) were 6.6 months (6 to 24 months ),median overall survival was 10.7 months. The majority of adverse reaction were nausea, vomiting, anorexia, diarrhea, leucopenia, alopecie. Most of them were Ⅰ/Ⅱ degree, only 6 cases reached III/IV degree. 3 cases had diarrhea with leucopenia and fever.Conclusions:The biweekly regimen of irinotcan in combination with 5-FU/LV results in significant and clinically meaningful improvement in survival and quality of life among patients with metastatic colorectal cancer. Toxicity is manageable.
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Background and purpose:The prognosis of high grade gliomas remains poor, and multidisciplinary treatment strategy has been much investigated recently. This study was to explore the efficacy of Temozolomide as first-line treatment combined with radiotherapy and followed by adjuvant chemotherapy for the treatment of newly diagnosed high grade gliomas. Methods:18 patients who had been pathologically proven to be high grade gliomas were enrolled into the study. The patients received 40 Gy/20fractions for the whole brain and followed by 20Gy/10fractions as a boost to tumor bed. All of the patients were given daily oral temozolomide 75mg/ m2 during radiotherapy. 4 weeks after radiotherapy, all of the patients received 6 cycles of Temozolomide, each cycle lasted 5 days with 28 days interval between each cycles. 150 mg/m2 of temozolomide was given for the first cycle for five days,followd by 200 mg/m2 of drug for the rest of the cycles if no significant drug related toxicities were observed. Results:Median follow-up was 12.5 months, 11 cases had either recurrence or progression, 5 of them died from the disease. The median time for disease progression-free survival was 9.8 months (95% CI, 6.1~9.8months), the median time for overall survival was 14 months (95% CI, 8.5 ~ 19.5months), 1-year overall survival rate was 55.6% ,6-month progression-free survival rate was 81.8%. there were no severe temozolomide related toxicities. Conclusion: Concurrent temozolomide with radiotherapy and followed by 6 cycles of temozolomide in the treatment of high grade gliomas had better clinical efficacy, the patients tolerated the strategy well and no severe toxicities were observed.