ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of metronomic chemotherapy of low dose phosphoramide combined with prednisolone (CP metronomic chemotherapy) on proliferation and apoptosis of RPMI 8226 cells, and to explore its regulating effect on Notch1/NF-κB signaling pathways.</p><p><b>METHODS</b>Experiment was divided into the DMSO control group, and the phosphoramide mustard (PM) group, the prednisolone group, the phosphoramide mustard plus prednisolone group (the CP group). RPMI 8226 cells were treated with different drugs, CCK-8 method was used to detect cell proliferation, flow cytometry was used to detect the cell cycle and apoptosis, reverse transcription PCR was used to detect Notch1 and NF-κB mRNA expression level.</p><p><b>RESULTS</b>Compared with DMSO control group, RPMI8226 cell proliferation inhibition rate in all the PM, prednisolone and CP groups increased significantly with prolonging of time (r of 0.994,0.996,0.999, respectively, P<0.001). And at the same time, the inhibitory rate of cell proliferation was significantly different; the cell inhibitory rate in PM group was lowest, that in CP group was highgest, that in prednissone group was intermediate (P<0.01). After 48 hours, compared with the DMSO control group, the G/Gcell proportion in treatment group increased significantly, S phase cell proportion decreased significantly, especially in PM and CP groups. The G/M phase cell proportion increased in PM group, while reduced in the prednisolone and the CP groups. After 48 hours, compared with the DMSO control group, RPMI 8226 cell apoptosis rate increased as follow: in PM, pre-dnisolone and CP group(P<0.01). After 48 hours, compared with the DMSO control group, Notch1 and NF-κB mRNA expression in the prednisolone, the PM and the CP group decreased significantly(P<0.001).</p><p><b>CONCLUSION</b>CP metronomic chemotherapy can significantly reduce RPMI 8226 cell proliferation, promote RPMI 8226 cell apoptosis, arrest RPMI 8226 cells mainly in the G/Gphase, and significantly reduce Notch1 and NF-κB expression levels. It is suggested that Notch1/NF-κB signaling pathways is involved in CP metronomic chemotherapy for MM.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.</p><p><b>METHODS</b>54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.</p><p><b>RESULTS</b>2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05).</p><p><b>CONCLUSIONS</b>Our findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Cyclophosphamide , Microvessels , Multiple Myeloma , Blood , Drug Therapy , Prednisone , Proto-Oncogene Proteins c-sis , Blood , Vascular Endothelial Growth Factor A , BloodABSTRACT
Objective To investigate the clinical effect of low-dose cyclophosphamide plus prednisone (CP regimen) in treatment of multiple myeloma (MM) and its influence on serum levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor BB (PDGF-BB). Methods Totally 54 patients with refractory or relapse MM were continuously treated with CP regimes oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). The peripheral blood samples were collected from each group 0, 2, 4, and 6 months after treatment. Serum VEGF and PDGF-BB levels were analyzed by ELISA. Results The overall effective rate was up to 69% (36/52) in our study. The treatment was effective in 30 patients, including 2 complete response (CR) cases, 4 very good partial response (VGPR) cases and 24 partial response (PR) cases, and their serum samples were examined for 4 times. The serum levels of VEGF and PDGF-BB were significantly decreased in the 30 patients at 2, 4, and 6 months after treatment (P<0. 01); while their levels were not significantly change in the 7 invalid patients 2 months after treatment compared with before treatment. Conclusion Low-dose cyclophosphamide plus prednisone has noticeable effect in treatment of MM patients; it can also greatly down-regulate serum VEGF and PDGF-BB levels. The mechanisms of CP regimen in MM patients may be associated with the inhibition of new blood vessel generation.
ABSTRACT
HCAP1 is a novel hepatic cancer related gene located on human chromosome 17p13.3. The loss of heterozygosity occurred at 17p13.3 in various human cancers. In order to investigate the effects of exogenous HCAP1 gene products on cell proliferation of T lymphoma Jurkat cell line, HCAP1 gene! was transfected into Jurkat cells mediated by liposome, and the cells stably expressing exogenous HCAP1 were screened with G418. The effects of HCAP1 products on cell proliferation were assessed by viable cell count, cell growth curve and colony formation assay in soft agar. The results showed that the HCAP1 transgenic Jurkat cells displayed slow growth rate, extended doubling time and reduced colony formation capability, as compared with the cells transfected with pBK/CMV empty vector (P < 0.01). It is concluded that exogenous HCAP1 gene products could inhibit the proliferation of Jurkat cells.