ZOLEDRONIC ACID INHIBITS CELL GROWTH OF MULTIPLE MYELOMA CELLS AND SHOWS SYNERGISTIC ANTIMYELOMA EFFECTS WITH BORTEZOMIB VIA DOWNREGULATION OF PIM-2 THROUGH NF-KB PATHWAY
(Abstract release date: 05/19/16)
EHA Library. Fu R. 06/09/16; 134843; PB1943
Dr. Rong Fu
Contributions
Contributions
Abstract
Abstract: PB1943
Type: Publication Only
Background
Recent studies showed that the third-generation biphosphonate Zoledronic acid (ZOL) can exhibit direct antitumour activity. However, its possible machnism remains unknown.
Aims
To explore the mechanism of Zol's antitumor activity.
Methods
In this study, RPMI-8226 cell line were treated with ZOL alone at various concentrations and combined with Bortezomib in vitro, then Cell proliferation, cell apoptosis, downsteam signaling pathway were detected by qRT-PCR and Western blot.
Results
We found that ZOL alone strongly inhibited proliferation of myeloma cells in vitro and induced their apoptosis. The same results were obtained in ZOL combined with Bortezomib after 24h. Futhermore, we found that Ras, pAKT and NF-kB were suppressed by ZOL alone and combined with Bortezomib at 24h. We demonstrated NF-Kb/pim-2 pathway which were also inhibited at 24h. However, it did not show the same results at 48h. additionally,NF-kB plays a pivotal role in regulating of pim-2 which proved by the result of downregulation of pim-2 was appered when the NF-kB inhibitor(Ro 106-9920) was used in RPMI-8226 cell line.
Conclusion
In conclusion, ZOL and the combination of ZOL with Bortezomib inhibited proliferation of myeloma cell via inhibiting NF-Kb/pim-2 pathway. Ras and pAkt were also inhibited. Combination of Zol with Bortezomib within 24 hours maybe more benefitial to alleviate tumour load in MM patients.
Session topic: E-poster
Keyword(s): Bortezomib, Myeloma, Zoledronate
Type: Publication Only
Background
Recent studies showed that the third-generation biphosphonate Zoledronic acid (ZOL) can exhibit direct antitumour activity. However, its possible machnism remains unknown.
Aims
To explore the mechanism of Zol's antitumor activity.
Methods
In this study, RPMI-8226 cell line were treated with ZOL alone at various concentrations and combined with Bortezomib in vitro, then Cell proliferation, cell apoptosis, downsteam signaling pathway were detected by qRT-PCR and Western blot.
Results
We found that ZOL alone strongly inhibited proliferation of myeloma cells in vitro and induced their apoptosis. The same results were obtained in ZOL combined with Bortezomib after 24h. Futhermore, we found that Ras, pAKT and NF-kB were suppressed by ZOL alone and combined with Bortezomib at 24h. We demonstrated NF-Kb/pim-2 pathway which were also inhibited at 24h. However, it did not show the same results at 48h. additionally,NF-kB plays a pivotal role in regulating of pim-2 which proved by the result of downregulation of pim-2 was appered when the NF-kB inhibitor(Ro 106-9920) was used in RPMI-8226 cell line.
Conclusion
In conclusion, ZOL and the combination of ZOL with Bortezomib inhibited proliferation of myeloma cell via inhibiting NF-Kb/pim-2 pathway. Ras and pAkt were also inhibited. Combination of Zol with Bortezomib within 24 hours maybe more benefitial to alleviate tumour load in MM patients.
Session topic: E-poster
Keyword(s): Bortezomib, Myeloma, Zoledronate
Abstract: PB1943
Type: Publication Only
Background
Recent studies showed that the third-generation biphosphonate Zoledronic acid (ZOL) can exhibit direct antitumour activity. However, its possible machnism remains unknown.
Aims
To explore the mechanism of Zol's antitumor activity.
Methods
In this study, RPMI-8226 cell line were treated with ZOL alone at various concentrations and combined with Bortezomib in vitro, then Cell proliferation, cell apoptosis, downsteam signaling pathway were detected by qRT-PCR and Western blot.
Results
We found that ZOL alone strongly inhibited proliferation of myeloma cells in vitro and induced their apoptosis. The same results were obtained in ZOL combined with Bortezomib after 24h. Futhermore, we found that Ras, pAKT and NF-kB were suppressed by ZOL alone and combined with Bortezomib at 24h. We demonstrated NF-Kb/pim-2 pathway which were also inhibited at 24h. However, it did not show the same results at 48h. additionally,NF-kB plays a pivotal role in regulating of pim-2 which proved by the result of downregulation of pim-2 was appered when the NF-kB inhibitor(Ro 106-9920) was used in RPMI-8226 cell line.
Conclusion
In conclusion, ZOL and the combination of ZOL with Bortezomib inhibited proliferation of myeloma cell via inhibiting NF-Kb/pim-2 pathway. Ras and pAkt were also inhibited. Combination of Zol with Bortezomib within 24 hours maybe more benefitial to alleviate tumour load in MM patients.
Session topic: E-poster
Keyword(s): Bortezomib, Myeloma, Zoledronate
Type: Publication Only
Background
Recent studies showed that the third-generation biphosphonate Zoledronic acid (ZOL) can exhibit direct antitumour activity. However, its possible machnism remains unknown.
Aims
To explore the mechanism of Zol's antitumor activity.
Methods
In this study, RPMI-8226 cell line were treated with ZOL alone at various concentrations and combined with Bortezomib in vitro, then Cell proliferation, cell apoptosis, downsteam signaling pathway were detected by qRT-PCR and Western blot.
Results
We found that ZOL alone strongly inhibited proliferation of myeloma cells in vitro and induced their apoptosis. The same results were obtained in ZOL combined with Bortezomib after 24h. Futhermore, we found that Ras, pAKT and NF-kB were suppressed by ZOL alone and combined with Bortezomib at 24h. We demonstrated NF-Kb/pim-2 pathway which were also inhibited at 24h. However, it did not show the same results at 48h. additionally,NF-kB plays a pivotal role in regulating of pim-2 which proved by the result of downregulation of pim-2 was appered when the NF-kB inhibitor(Ro 106-9920) was used in RPMI-8226 cell line.
Conclusion
In conclusion, ZOL and the combination of ZOL with Bortezomib inhibited proliferation of myeloma cell via inhibiting NF-Kb/pim-2 pathway. Ras and pAkt were also inhibited. Combination of Zol with Bortezomib within 24 hours maybe more benefitial to alleviate tumour load in MM patients.
Session topic: E-poster
Keyword(s): Bortezomib, Myeloma, Zoledronate
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