TY - JOUR
T1 - A combination of paclitaxel and siRNA-mediated silencing of Stathmin inhibits growth and promotes apoptosis of nasopharyngeal carcinoma cells
AU - Wu, Yong
AU - Tang, Min
AU - Wu, Yuan
AU - Weng, Xinxian
AU - Yang, Lifang
AU - Xu, Wen
AU - Yi, Wie
AU - Gao, Jinghe
AU - Bode, Ann M.
AU - Dong, Zigang
AU - Cao, Ya
N1 - Funding Information:
This work was supported by the National Basic Research Program of China (973 Program) (2009CB521801 and 2011CB504305).
PY - 2014/2
Y1 - 2014/2
N2 - Background: Stathmin, a microtubule associated protein (MAP), is an important molecular target for cancer therapy. Paclitaxel is one of the primary antitumor drugs targeting microtubules (MTs). We hypothesized that decreasing the expression level of Stathmin might improve the effectiveness of paclitaxel in the treatment of nasopharyngeal carcinoma (NPC). Methods: NPC cell lines, CNE1-LMP1 and HNE2, and a CNE1-LMP1 tumor xenograft mouse model were used to test both in vitro and in vivo our siRNA-based Stathmin silencing strategy. The effects of Stathmin silencing on cell proliferation, apoptosis, and viability were investigated using MTT, AO/EB staining, TUNEL, caspase protein detection, and FCM assays. Cell migration and invasion were assayed using a Transwell assay. The combined effects of Stathmin silencing and paclitaxel were investigated using MTT, FCM, Western blot and indirect immunofluorescence assays. The effect of paclitaxel on Stathmin expression in NPC cells and, in addition, A375, MGC and HeLa cells was determined by RT-PCR and Western blotting. Results: We found that siRNA-mediated silencing of Stathmin suppresses proliferation, induces apoptosis through the mitochondrial pathway, and causes G2/M-phase cell cycle arrest in the NPC cell lines CNE1-LMP1 and HNE2. Also, the migration and invasion of the respective NPC cells were found to be inhibited. In addition, we show that a combination of Stathmin silencing and paclitaxel is more effective than either agent alone in inhibiting proliferation and inducing apoptosis, cell cycle arrest, and MT polymerization. Furthermore, we found that Stathmin expression in the tumor cells is down-regulated by paclitaxel treatment. Conclusion: siRNA-mediated silencing of Stathmin suppresses the proliferation, invasion and metastasis, and induces the apoptosis of NPC cells. Paclitaxel reduces the expression of Stathmin, and combining Stathmin silencing with paclitaxel treatment enhances MT polymerization. This combined strategy may provide a new approach for clinical NPC treatment.
AB - Background: Stathmin, a microtubule associated protein (MAP), is an important molecular target for cancer therapy. Paclitaxel is one of the primary antitumor drugs targeting microtubules (MTs). We hypothesized that decreasing the expression level of Stathmin might improve the effectiveness of paclitaxel in the treatment of nasopharyngeal carcinoma (NPC). Methods: NPC cell lines, CNE1-LMP1 and HNE2, and a CNE1-LMP1 tumor xenograft mouse model were used to test both in vitro and in vivo our siRNA-based Stathmin silencing strategy. The effects of Stathmin silencing on cell proliferation, apoptosis, and viability were investigated using MTT, AO/EB staining, TUNEL, caspase protein detection, and FCM assays. Cell migration and invasion were assayed using a Transwell assay. The combined effects of Stathmin silencing and paclitaxel were investigated using MTT, FCM, Western blot and indirect immunofluorescence assays. The effect of paclitaxel on Stathmin expression in NPC cells and, in addition, A375, MGC and HeLa cells was determined by RT-PCR and Western blotting. Results: We found that siRNA-mediated silencing of Stathmin suppresses proliferation, induces apoptosis through the mitochondrial pathway, and causes G2/M-phase cell cycle arrest in the NPC cell lines CNE1-LMP1 and HNE2. Also, the migration and invasion of the respective NPC cells were found to be inhibited. In addition, we show that a combination of Stathmin silencing and paclitaxel is more effective than either agent alone in inhibiting proliferation and inducing apoptosis, cell cycle arrest, and MT polymerization. Furthermore, we found that Stathmin expression in the tumor cells is down-regulated by paclitaxel treatment. Conclusion: siRNA-mediated silencing of Stathmin suppresses the proliferation, invasion and metastasis, and induces the apoptosis of NPC cells. Paclitaxel reduces the expression of Stathmin, and combining Stathmin silencing with paclitaxel treatment enhances MT polymerization. This combined strategy may provide a new approach for clinical NPC treatment.
KW - Microtubule
KW - Nasopharyngeal carcinoma
KW - Paclitaxel
KW - Stathmin
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=84894498104&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84894498104&partnerID=8YFLogxK
U2 - 10.1007/s13402-013-0163-3
DO - 10.1007/s13402-013-0163-3
M3 - Article
C2 - 24306928
AN - SCOPUS:84894498104
VL - 37
SP - 53
EP - 67
JO - Cellular oncology (Dordrecht)
JF - Cellular oncology (Dordrecht)
SN - 1570-5870
IS - 1
ER -
