Selective cyclo-oxygenase-2 (CQX-2) inhibitor, VIOXX (rofecoxib), wasvoluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on September 30,2004, for its potential lethal side effects of he...Selective cyclo-oxygenase-2 (CQX-2) inhibitor, VIOXX (rofecoxib), wasvoluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on September 30,2004, for its potential lethal side effects of heart attack or stroke, The Merck' s decision wasbased on new, three-year data from a prospective, multi-center, randomized, placebo-controlled,double-blind clinical trial of VIOXX with an unrelated study, the APPROVe (Adenomatous PolypPrevention on VIOXX) trial. The trial has been enrolling 2 600 patients and comparing 156 weeks(three years) of treatment with VIOXX 25 mg to placebo since 2000.展开更多
Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor（ER）, progesterone receptor（PR） and human epidermal growth factor receptor-2（HER2）. A regular chemotherapy cannot eradicate t...Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor（ER）, progesterone receptor（PR） and human epidermal growth factor receptor-2（HER2）. A regular chemotherapy cannot eradicate triple-negative breast cancer. In the present study, we aimed to develop a combined use of daunorubicin and rofecoxib to treat triple-negative breast cancer, and reveal the underlying mechanisms. A gradient elution HPLC-UV method was developed for quantification, and the evaluations were performed on the triple-negative breast cancer MDA-MB-231 cells using a high content screening system. The results demonstrated that daunorubicin alone was insensitive to the triple negative breast cancer cells, while the combined use of daunorubicin and rofecoxib was able to effectively kill these triple-negative cancer cells, exhibiting a rofecoxib concentration-dependent manner. The mechanism revealed that the augmented anticancer efficacy was associated with direct killing effect, inducing apoptosis and inducing autophagy by the combination treatment. Besides, the apoptosis signaling pathways were correlated to a cascade of reactions by activating apoptotic enzyme caspase family and by suppressing anti-apoptotic gene expressed protein Bcl-2 family. In conclusion, this study provided a fundamental evidence for further developing the combined use of daunorubicin and rofecoxib formulation, hence offering a promising strategy for eradicating the triple negative breast cancer.展开更多
文摘Selective cyclo-oxygenase-2 (CQX-2) inhibitor, VIOXX (rofecoxib), wasvoluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on September 30,2004, for its potential lethal side effects of heart attack or stroke, The Merck' s decision wasbased on new, three-year data from a prospective, multi-center, randomized, placebo-controlled,double-blind clinical trial of VIOXX with an unrelated study, the APPROVe (Adenomatous PolypPrevention on VIOXX) trial. The trial has been enrolling 2 600 patients and comparing 156 weeks(three years) of treatment with VIOXX 25 mg to placebo since 2000.
基金National Natural Science Foundation of China(Grant No.81373343)the Key Grant of Beijing Natural Science Foundation(Grant No.7131009)
文摘Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor（ER）, progesterone receptor（PR） and human epidermal growth factor receptor-2（HER2）. A regular chemotherapy cannot eradicate triple-negative breast cancer. In the present study, we aimed to develop a combined use of daunorubicin and rofecoxib to treat triple-negative breast cancer, and reveal the underlying mechanisms. A gradient elution HPLC-UV method was developed for quantification, and the evaluations were performed on the triple-negative breast cancer MDA-MB-231 cells using a high content screening system. The results demonstrated that daunorubicin alone was insensitive to the triple negative breast cancer cells, while the combined use of daunorubicin and rofecoxib was able to effectively kill these triple-negative cancer cells, exhibiting a rofecoxib concentration-dependent manner. The mechanism revealed that the augmented anticancer efficacy was associated with direct killing effect, inducing apoptosis and inducing autophagy by the combination treatment. Besides, the apoptosis signaling pathways were correlated to a cascade of reactions by activating apoptotic enzyme caspase family and by suppressing anti-apoptotic gene expressed protein Bcl-2 family. In conclusion, this study provided a fundamental evidence for further developing the combined use of daunorubicin and rofecoxib formulation, hence offering a promising strategy for eradicating the triple negative breast cancer.
