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Study on the Effects of Homoharringtonine to Acute Promyelocytic Leukemia Cell Line-NB4 Cells

Author: MaoLiPing
Tutor: JinJie
School: Zhejiang University
Course: Internal Medicine
Keywords: Homoharringtonine base Acute promyelocytic leukemia Cytarabine PML / RARa
CLC: R733.7
Type: Master's thesis
Year: 2007
Downloads: 31
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Abstract


[Objective acute promyelocytic leukemia (acute promyelocytic leukemia, APL) is a special subtype of acute myelogenous leukemia, acute myeloid leukemia accounts for about 5% -20%. Which is characterized by severe bleeding tendency, hyperthyroidism complicated by DIC and secondary or primary fibrinolysis, often leads to the early death of the patients. Due to the application of all-trans retinoic acid and arsenic trioxide greatly improved the prognosis of APL. ATRA alone to treat high recurrence rate and recurrence of the resistance is gradually understanding. Remission after chemotherapy with anthracyclines as consolidation therapy long-term survival rate of up to 92%. Anthracycline cardiac side effects, and the heart of cumulative toxicity. It does not apply to elderly patients, patients with existing heart disease or in combination with other drugs may be toxic to the heart patients. The homoharringtonine alkali (homharringtonine, HHT) to the case of a total plant alkaloids isolated alkaloids from Cephalotaxus. Cytarabine as anti-metabolic drugs, combined with a synergistic effect with other chemotherapy drugs. This experimental study homoharringtonine alkali and cytarabine NB4 cell line and to explore its mechanism to provide a theoretical basis for the clinical. 【Methods】 1. HHT and Ara-c NB4 cell line in vitro growth inhibition by MTT colorimetric assay. 2.RealTime-PCR to detect the the HHT role NB4 Acute promyelocytic leukemia fusion gene PML / RARa expression characteristic 【Results】 1 drugs on cell growth inhibition 1.1 HHT showed a time-dependent growth inhibition of NB4 cell line The MTT colorimetric detection results processing the NB4 cells 24hr, 48hr, 72hr 0-320ng/ml HHT. HHT inhibited the growth of NB4 cells was time-dependent, significant differences between groups (P value less than 0.001). In the same action time, each concentration group showed no significant difference (P> 0.05). A role in time, the differences between each concentration group significant cell growth inhibition rate and time-dependent, weighted linear regression method, 24hr, 48hr, 72hr half inhibitory concentration (the the IC 50 ) respectively. for: 420.059ng/ml, 103.008ng/ml, 31.628ng/ml. 1.2 Ara-C NB4 cell growth inhibition was concentration-dependent 0-3.5ug/mlAra-c processing NB4 cells 24 hr. Ara-c inhibited the growth of NB4 cells in a concentration-dependent manner in the same action time, each concentration group asked the difference was statistically significant, P values ??were less than 0.05. The calculated weighted linear regression method, 24hr half inhibitory concentration (IC50) as follows: 15.3ug/ml. 1.3 Ara-C with HHT associated with NB4 cell growth inhibition synergies 20ng/ml, 40ng/ml the HHT United 1ug/mlAra-c processing NB4 cells 24 hr. Ara-c and HHT NB4 cells were inhibited the growth and Ara-c synergies with HHT. 2 HHT at the transcriptional level by down-regulating PML / RARα fusion gene expression of anti-tumor role 0ng/ml, 20ng/ml, 40ng/ml HHT treatment NB4 cells 24hr RealTime-PCR technology to detect the level of the PML / RAR. Different concentration of HHT can cut PML / RARα level. Suggesting that HHT Department at the transcriptional level by down-regulating PML / RARα fusion gene expression to achieve the purpose of anti-tumor. [Conclusion] 1.HHT on NB4 cell line inhibited, and was time-dependent. 2.Ara-c with HHT have synergistic anti-tumor effect. 3.HHT down at the transcriptional level by acting PML / RARα fusion gene expression pathways to achieve the anti-tumor effect.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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