Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cis...Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.展开更多
BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head(ONFH),although significant adverse reactions often follow long-term use.Extracor...BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head(ONFH),although significant adverse reactions often follow long-term use.Extracorporeal shock wave therapy(ESWT)can delay the progression of ONFH,alleviate the pain and functional limitations it causes,and avoid the adverse effects of celecoxib.AIM To investigate the effects of individual ESWT,a treatment alternative to the use of celecoxib,in alleviating pain and dysfunction caused by ONFH.METHODS This was a randomized,controlled,double-blinded,non-inferiority trial.We examined 80 patients for eligibility in this study;8 patients were excluded based on inclusion and exclusion criteria.A total of 72 subjects with ONFH were randomly assigned to group A(n=36;celecoxib+alendronate+sham-placebo shock wave)or group B(n=36;individual focused shock wave[ESWT based on magnetic resonance imaging three-dimensional(MRI-3D)reconstruction]+alendronate).The outcomes were assessed at baseline,at the end of treatment,and at an 8-wk follow-up.The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score(HHS)(improvement of 10 points or more from the baseline was deemed sufficient).Secondary outcome measures were post-treatment HHS,visual analog scale(VAS),and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores.RESULTS After treatment,the pain treatment efficiency of group B was greater than that of group A(69%vs 51%;95%CI:4.56%to 40.56%),with non-inferiority thresholds of-4.56%and-10%,respectively.Furthermore,the HHS,WOMAC,and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A(P<0.001).After therapy,the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk(P<0.001),although HHS was only significantly altered at the 2 wk point(P<0.001).On the 1st d and 2nd wk after treatment,HHS and VAS scores were different between groups,with the difference in HHS lasting until week 4.Neither group had severe complications such as skin ulcer infection or lower limb motorsensory disturbance.CONCLUSION Individual shock wave therapy(ESWT)based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.展开更多
基金the Beijing Municipal Science and Technology Commission(grant Z211100002921013)the Tongzhou District Science and Technology Committee Project to Tongzhou(grant KJ2020CX010).
文摘Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.
文摘BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head(ONFH),although significant adverse reactions often follow long-term use.Extracorporeal shock wave therapy(ESWT)can delay the progression of ONFH,alleviate the pain and functional limitations it causes,and avoid the adverse effects of celecoxib.AIM To investigate the effects of individual ESWT,a treatment alternative to the use of celecoxib,in alleviating pain and dysfunction caused by ONFH.METHODS This was a randomized,controlled,double-blinded,non-inferiority trial.We examined 80 patients for eligibility in this study;8 patients were excluded based on inclusion and exclusion criteria.A total of 72 subjects with ONFH were randomly assigned to group A(n=36;celecoxib+alendronate+sham-placebo shock wave)or group B(n=36;individual focused shock wave[ESWT based on magnetic resonance imaging three-dimensional(MRI-3D)reconstruction]+alendronate).The outcomes were assessed at baseline,at the end of treatment,and at an 8-wk follow-up.The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score(HHS)(improvement of 10 points or more from the baseline was deemed sufficient).Secondary outcome measures were post-treatment HHS,visual analog scale(VAS),and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores.RESULTS After treatment,the pain treatment efficiency of group B was greater than that of group A(69%vs 51%;95%CI:4.56%to 40.56%),with non-inferiority thresholds of-4.56%and-10%,respectively.Furthermore,the HHS,WOMAC,and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A(P<0.001).After therapy,the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk(P<0.001),although HHS was only significantly altered at the 2 wk point(P<0.001).On the 1st d and 2nd wk after treatment,HHS and VAS scores were different between groups,with the difference in HHS lasting until week 4.Neither group had severe complications such as skin ulcer infection or lower limb motorsensory disturbance.CONCLUSION Individual shock wave therapy(ESWT)based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.
