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Research Article
yize bian
Fujian Medical University
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Context: It is urgent to develop drugs with independent intellectual property rights and more reasonable price, safe and effective treatment of RA.
Objective: To study the inhibitory effect of curcumin derivative FM0807 on the proliferation of RA-FLS cells and its possible mechanism.
Materials&Methods: Rheumatiod arthritis fibroblast-like synoviocyte (RA-FLS) were cultured in alone or in the presence of FM0807 (25μM, 50μM and 100μM). MTT method was used to analyze the effect of cell proliferation, Hoechst 33342/PI staining was used to observe the effect of apoptosis. Cell migration assay was used to observe the effect of migration ability of RA-FLS. The expression of JAK2,STAT3, IL-6 and IL-1β gene was determined by RT-PCR method. Western blotting assay was used to detect the expression of JAK2-STAT3 signaling pathway related proteins.
Results: A 72-hour exposure FM0807 result in cell proliferation inhibition significantly(IC50=41.38μM). The migration of RA-FLS is inhibited by FM0807 100µM in 72 h (P<0 05). High Content Screening showed that the apoptosis rate of RA-FLS was up regulated after treated FM0807. Presence of FM0807 in the culture medium strongly inhibited JAK2,STAT3,IL-6 and IL-1βmRNA expression in a concentration-dependent manner. Western blot demonstrated a substantially reduced protein expression of phosphorylation of JAK2 and STAT3. At the same time, the anti-apoptotic protein Bcl-2 and the key proteins of PI3K cell pathway including Akt and mTOR were down-regulated. on the contrary, the expression of apoptosis execution protein Cleaved-caspase3 and Bax were up-regulated.
Conclusion: Curcumin derivative FM0807 may inhibit the proliferation of RA-FLS and promote its apoptosis by inhibiting JAK2-STAT3 signaling pathway.
Keywords
Rheumatoid arthritis, proliferation, migration, inflammatory, apoptosis
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
yize bian
Fujian Medical University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 06 Apr, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Context: It is urgent to develop drugs with independent intellectual property rights and more reasonable price, safe and effective treatment of RA.
Objective: To study the inhibitory effect of curcumin derivative FM0807 on the proliferation of RA-FLS cells and its possible mechanism.
Materials&Methods: Rheumatiod arthritis fibroblast-like synoviocyte (RA-FLS) were cultured in alone or in the presence of FM0807 (25μM, 50μM and 100μM). MTT method was used to analyze the effect of cell proliferation, Hoechst 33342/PI staining was used to observe the effect of apoptosis. Cell migration assay was used to observe the effect of migration ability of RA-FLS. The expression of JAK2,STAT3, IL-6 and IL-1β gene was determined by RT-PCR method. Western blotting assay was used to detect the expression of JAK2-STAT3 signaling pathway related proteins.
Results: A 72-hour exposure FM0807 result in cell proliferation inhibition significantly(IC50=41.38μM). The migration of RA-FLS is inhibited by FM0807 100µM in 72 h (P<0 05). High Content Screening showed that the apoptosis rate of RA-FLS was up regulated after treated FM0807. Presence of FM0807 in the culture medium strongly inhibited JAK2,STAT3,IL-6 and IL-1βmRNA expression in a concentration-dependent manner. Western blot demonstrated a substantially reduced protein expression of phosphorylation of JAK2 and STAT3. At the same time, the anti-apoptotic protein Bcl-2 and the key proteins of PI3K cell pathway including Akt and mTOR were down-regulated. on the contrary, the expression of apoptosis execution protein Cleaved-caspase3 and Bax were up-regulated.
Conclusion: Curcumin derivative FM0807 may inhibit the proliferation of RA-FLS and promote its apoptosis by inhibiting JAK2-STAT3 signaling pathway.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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