CN104721186A - Application of pravastatin (PRAV) to preparation of medicine for promoting apoptosis of human lung adenocarcinoma A549 cells - Google Patents

Application of pravastatin (PRAV) to preparation of medicine for promoting apoptosis of human lung adenocarcinoma A549 cells Download PDF

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CN104721186A
CN104721186A CN201510136611.3A CN201510136611A CN104721186A CN 104721186 A CN104721186 A CN 104721186A CN 201510136611 A CN201510136611 A CN 201510136611A CN 104721186 A CN104721186 A CN 104721186A
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apoptosis
pravastatin
medicine
lung adenocarcinoma
preparation
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张春娣
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Qiqihar Medical University
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Qiqihar Medical University
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Abstract

The invention relates to application of pravastatin (PRAV) to preparation of a medicine for promoting the apoptosis of human lung adenocarcinoma A549 cells and mainly aims to solve the problem of insignificant effects of chemotherapy on lung adenocarcinoma. The invention is characterized by the application of pravastatin (PRAV) to preparation of a medicine for promoting the apoptosis of human lung adenocarcinoma A549 cells. PRAV can be used for effectively inhibiting the proliferation of lung cancer cells in vitro and inducing the apoptosis of human lung adenocarcinoma A549 cells, can be used for improving the sensitivity of chemotherapeutic medicines and can assist chemotherapeutic medicines in inhibiting tumors.

Description

Pravastatin is for the preparation of the application for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine
Technical field:
The present invention relates to the purposes field of pravastatin for the preparation of medicine, especially a kind of pravastatin is for the preparation of the application for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine.
Background technology:
Pulmonary carcinoma is one of major malignant tumor threatening human health, the annual new cases about 1,600,000 in the whole world.Along with the change of China's spectrum of disease, pulmonary carcinoma has become China's town and country mortality of malignant tumors first cause, accounts for 22.7% of whole mortality of malignant tumors.Modal is clinically nonsmall-cell lung cancer (non-small cell lung cancer, NLCSC), account for 80% of all pulmonary carcinoma, and adenocarcinoma of lung sickness rate constantly increases from last century Mo, replace lung squamous cancer at present, become modal histological type.Adenocarcinoma of lung, because its incubation period is longer, when making a definite diagnosis, patient many places are the late period of cancer, and in recent years along with the increase gradually of people's life stress, the sickness rate of advanced pulmonary adenocarcinoma presents the trend risen year by year, which results in the great attention of academia to it, therefore find medicine safely and effectively, to treat advanced pulmonary adenocarcinoma, there is great clinical meaning.In the forming process of malignant tumor, the expression of gene participating in apoptosis plays key player.The sudden change of apoptosis-related genes, disappearance or overexpression, can cause apoptosis obstacle or infinite multiplication relatively, thus lead oncogenic generations development and to chemotherapeutics generation drug resistance.Therefore, the how expression of Effective Regulation apoptosis-related genes or its product, promotes apoptosis of tumor cells, is improve the efficient key point of oncotherapy.Chemotherapy occupies consequence in Treatment for Non-small Cell Lung, but multidrug resistance and adverse effect comparatively generally affect its curative effect.
At present, the cause of disease of pulmonary carcinoma and pathogenesis are illustrated not yet completely in the world, but from angle, the propagation of cancerous cell and the abnormal to the growth of cell and playing an important role of tumor of apoptosis of oncocytology.The death of malignant cell and the equal defectiveness of apoptosis compared with normal cell, and Apoptosis inhibitor often causes growth of tumour cell out of control in tumor cell.Apoptosis is the basic biological phenomena of one of cell, has important biological significance and the Molecular Biology Mechanism of complexity, plays an important role in the forming process of malignant tumor.Apoptosis is the active death process of cell, and it is one of important mechanisms of tumorigenesis that apoptosis is escaped, and promotes that apoptosis is a kind of important mechanisms of antineoplastic.The same with cell proliferation, apoptosis is also the accurate process by gene regulation, mainly contains 2 approach: activate caspase-3 (Caspase-3) by the death receptor on cell membrane and cause apoptosis; Activate Caspase-9 by cytochrome C release in kytoplasm mitochondrial, and then activation Caspase-3 promotes apoptosis.BCL-2 family protein member participates in regulating apoptotic generation, is regulatory factor important in apoptotic process.These albumen are mainly distributed in the endomembrane system of cell, mitochondrial inner membrane and nuclear membrane distribute especially abundant.BCL-2 family gene is divided into 2 classes: a class promotes that apoptogene is as BAX, and a class presses down apoptogene as BAX-2.Therefore the destiny of cell depends on and the ratio of the homology that formed and heterodimer between mitochondrial inner membrane surface BCL-2 family anti-apoptotic and short apoptosis member.Although the induced factor of apoptosis is varied, all must by the apoptosis pathway regulating the expression of apoptogene (short apoptogene and apoptosis inhibit gene) to come active cell inside.Once this path is activated, the generation of apoptosis will be irreversible.
Summary of the invention:
The invention reside in and overcome Problems existing in background technology, and provide a kind of pravastatin for the preparation of the new opplication for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine.Pravastatin effectively can suppress the in-vitro multiplication of lung carcinoma cell, and induction apoptosis of human lung adenocarcinoma A 549, can also strengthen the sensitivity of chemotherapeutics.
The present invention solves its problem and reaches by following technical scheme: a kind of pravastatin is for the preparation of the application for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine.
Described pravastatin can also for the preparation of the application of adjuvant therapy of tumors medicine; The patient increased blood fat is more applicable, plays primary prevention and secondary prevention effect to coronary heart disease.
Described consumption is 20mg/d; The highest use can arrive 40mg/d; 1 time on the one, administering mode is oral, takes before liking to sleep most.
Statins is the competitive inhibitor of the rate-limiting enzyme HMG-CoA reductase of cholesterol biosynthesis, active by reducing HMG-CoA reductase, reduce synthesis and retardance methylol valeric acid (MVA) approach of intracellular cholesteryl, suppress kinds of tumor cells propagation, differentiation-inducing and apoptosis.
Pravastatin (PRAV) is the competitive inhibitor of 3-hydroxyl 3-methyl glutaryl coenzyme A (HMG-CoA) reductase, it suppresses the synthesis of cholesterol by the rate-limiting enzyme HMG-CoA reductase in reversible inhibition Biosynthesis of cholesterol process, reduces LDL level in blood.And PRAV is the one of Statins, the sensitivity of cancerous cell to chemotherapy can be strengthened, except effect for reducing fat, also have simultaneously and reverse Endothelial Dysfunction, immunity moderation function, effect such as pleiotropy such as minimizing ventricular arrhythmia and thrombosis etc.To tumor cell, there is Inhibit proliferaton, differentiation-inducing or apoptosis, suppression blood vessel occur, reduce the effects such as invasive ability.Statins all has remarkable inhibitory action to multiple cancerous cell such as carcinoma of prostate, cancer of pancreas, melanoma, bladder cancer and breast carcinoma, and it is little to normal impact cell, it is the more potential antitumor drug of one, affect very little, if some cancer patients increases with blood fat simultaneously, apply this medicine will effect better.
The present invention can have following beneficial effect compared with above-mentioned background technology: this pravastatin is for the preparation of the application for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine, pravastatin effectively can suppress the in-vitro multiplication of lung carcinoma cell, and in time dependence and concentration dependent; PRAV can also strengthen the sensitivity of chemotherapeutics, also has adjunct antineoplastic effect.This medicine can tentatively be applied to clinical, adjuvant therapy of tumors, especially nonsmall-cell lung cancer, and the patient increased blood fat is more applicable.
Accompanying drawing illustrates:
Accompanying drawing 1 is the picture of Lung Adenocarcinoma A 549 Cell under optical microscope of the present invention.
Detailed description of the invention:
Below in conjunction with specific embodiment, the invention will be further described:
Embodiment 1
Purchaser's lung adenocarcinoma cells A549, carry out external cellar culture, the collecting cell when exponential phase, Methyl thiazoly tetrazolium assay (tetrzolium-based colorimetric assay, MTT) method is adopted to detect 0umol/L, 5umol/L, 10umol/L, 20umol/L, 40umol/L concentration group and (24h, 48h, 72h) time group PRAV impact on cell survival and growth.Application flow cytometer (flow cytometry, FCM) measures three time points, and the PRAV of variable concentrations is on the impact of A549 cell cycle distribution and apoptosis.Here is the optical microscope picture of Lung Adenocarcinoma A 549 Cell, sees Fig. 1.PRAV variable concentrations and action time on the apoptotic impact of A549 in table 1.
The suppression ratio (x ± s) of the lower A549 cell of table 1PRAV effect
Table 1 is visible, and the same time compares P < 0.05 with matched group; Same concentration compares P < 0.01 with 24h
Flow cytomery apoptosis rate result shows, PRAV has obvious intervention effect to apoptosis, percentage rate increases with PRAV concentration and increases, with matched group (non-dosing group) comparing difference, there is significance (P<0.05), and have obvious time dependence, action time is longer, affects larger.
From above-described embodiment, pravastatin effectively can suppress the in-vitro multiplication of lung carcinoma cell, and in time dependence and concentration dependent; Inducing its tune to die may be one of mechanism of pravastatin antitumaous effect.PRAV can also strengthen the sensitivity of chemotherapeutics in addition, also has adjunct antineoplastic effect.This medicine can tentatively be applied to clinical, adjuvant therapy of tumors, and the patient increased blood fat is more applicable.
Case 1: patient week so-and-so, man, 58 years old, Daqing, Heilongjiang Province, suffer from adenocarcinoma of lung, patient has hyperlipidemia simultaneously, likes edible animal meat and long-term alcohol, suffers from adenocarcinoma of lung and be admitted to hospital, symptom: Progressive symmetric erythrokeratodermia dyspnea, cough, the display of outpatient service perspective, bilateral pleural effusion, the chemotherapy regimen treatment of application pemetrexed+cisplatin, and intrathecal anticarcinogen, take pravastatin treatment hyperlipidemia simultaneously, after 2 months, hydrothorax disappears, and the symptoms such as cough alleviate, breast lesion reduces, and alleviation is left hospital, without recurrence.
Case 2: patient Lee so-and-so, female, 57 years old, Qiqihaer City of Heilongjiang Province, local Diagnosis of pulmonary adenocarcinoma, suffered from serious blood fat high simultaneously, is in and takes the general Liprevil of blood lipid-lowering medicine always.Symptom: Progressive symmetric erythrokeratodermia dyspnea, supraclavicular lymph nodes enlargement, and with spitting of blood, inappetence, continues after being admitted to hospital to take pravastatin treatment hyperlipidemia, the chemotherapy regimen treatment of application pemetrexed+cisplatin, through the treatment of 2 months, patients symptomatic obviously alleviated, and left hospital after 3 months.

Claims (4)

1. a pravastatin is for the preparation of the application for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine.
2. pravastatin according to claim 1 is for the preparation of the application for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine, it is characterized in that: described pravastatin can also for the preparation of the application of adjuvant therapy of tumors medicine.
3. pravastatin according to claim 1 is used for auxiliary treatment apoptosis of human lung adenocarcinoma A 549, it is characterized in that: the patient that described pravastatin increases blood fat is more applicable, plays primary prevention and secondary prevention effect to coronary heart disease.
4. the pravastatin according to claim 1 or 2 or 3 is for the preparation of the application for the treatment of apoptosis of human lung adenocarcinoma A 549 medicine, and it is characterized in that: consumption is 20mg/d, 1 time on the one, administering mode is oral.
CN201510136611.3A 2015-03-26 2015-03-26 Application of pravastatin (PRAV) to preparation of medicine for promoting apoptosis of human lung adenocarcinoma A549 cells Pending CN104721186A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005000208A2 (en) * 2003-05-30 2005-01-06 Combinatorx, Inc. Combination therapy for the treatment of neoplasms
CN1980662A (en) * 2004-07-01 2007-06-13 默克公司 Mitotic kinesin inhibitors

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005000208A2 (en) * 2003-05-30 2005-01-06 Combinatorx, Inc. Combination therapy for the treatment of neoplasms
CN1980662A (en) * 2004-07-01 2007-06-13 默克公司 Mitotic kinesin inhibitors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YA-FAN YEH ETC.: "Enhancing Effect of Dietary Cholesterol and Inhibitory Effect of Pravastatin on Allergic Pulmonary Inflammation", 《JOURNAL OF BIOMEDICAL SCIENCE》 *

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