CN103536607A - Anti-tumor effects of oxytetracycline, propafenone and dipyrone - Google Patents
Anti-tumor effects of oxytetracycline, propafenone and dipyrone Download PDFInfo
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- CN103536607A CN103536607A CN201210251287.6A CN201210251287A CN103536607A CN 103536607 A CN103536607 A CN 103536607A CN 201210251287 A CN201210251287 A CN 201210251287A CN 103536607 A CN103536607 A CN 103536607A
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Abstract
The invention relates to three non-clinical antitumor drugs which are found to have anti-tumor effects and mainly can inhibit the proliferation of lung cancer A549 cells or cervical cancer Hela cells. The technical problem to be solved is that some clinical drugs are screened by using the lung cancer A549 cells and the cervical cancer Hela cells, so as to obtain the non-clinical antitumor drugs with the antitumor effects. Key points of technical schemes for solving the problems are as follows: the lung cancer A549 cells and the cervical cancer Hela cells are processed for 48 hours by using drugs of saturated concentration, and the changes of the morphology and quantity of the cells are observed by a microscope; for drugs with inhibitory actions, survival rate and LDH (Lactate Dehydrogenase) activity detection is further carried out on the cells, and Hoechst33258 is applied to cell apoptosis detection. Main purposes: the non-clinical anticancer drugs for remarkably inhibiting the proliferation of the lung cancer A549 cells or cervical cancer Hela cells are found and are applied to the clinical treatment of patients with lung cancer or cervical cancer.
Description
Technical field
The present invention relates to the new function of the antitumor action of three kinds of medicines.Specifically, the present invention relates to three kinds of non-clinical antitumor drug, be found to have antitumor action, is mainly the propagation that can significantly suppress lung cancer A549 cell or cervical cancer Hela cell.
Background technology
Clinical trial is last ring of new drug development, and it need to spend huge fund fund.Old medicine is use newly, particularly finds that " old medicine " through long-term clinical practice application has the meaning of new purposes very huge, and it is worth never lower than a kind of new drug of discovery.At present almost do not have a kind of medicine can reach cancer patients' such as curing pulmonary carcinoma or cervical cancer completely function, therefore, it is vital finding a kind of new type antineoplastic medicine effective, special, that toxic and side effects is little.
The new purposes of a lot of old medicines is all that clinician finds in clinical practice, has larger occasionality.If consciously, in a planned way detect the new purposes of some clinical applications, just may find more their new purposes quickly, be applied to clinically, can alleviate the slight illness of even removing patient, can produce very large Social benefit and economic benefit.This is a kind of approach of effective and thrifty discovery new drug.
Oxytetracycline (oxytetracycline), Propafenone (propafenone) and dipyrone (metamizol; Dipyrone) etc. medicine clinical antitumor drug of right and wrong all, utilizes Lung Adenocarcinoma A 549 Cell and these clinical applications of cervical cancer Hela cell screening, may find the new purposes of their antitumor actions.
Summary of the invention
Find first in the world in the present invention oxytetracycline, these non-clinical antitumor drug of Propafenone and dipyrone, have antitumor action.Specifically, oxytetracycline, Propafenone and dipyrone can both significantly suppress the propagation of Lung Adenocarcinoma A 549 Cell, and only have the significantly propagation of cervical cancer inhibiting Hela cell of Propafenone.
Oxytetracycline, Propafenone and the dipyrone inhibitory action to lung cancer A549 cell or cervical cancer Hela cells survival rate.Working concentration is the oxytetracycline of 0.005g/L to 0.2g/L, Propafenone or dipyrone, process respectively lung cancer A549 cell or cervical cancer Hela cell 48h, application SRB method detects cell survival rate, result shows, the survival rate of the remarkable cervical cancer inhibiting Hela of the mode cell that Propafenone can rely on concentration, and oxytetracycline and dipyrone inhibitory action not significantly (Figure 1A).The mode that these three kinds of medicines can both rely on concentration significantly suppresses the survival rate (Figure 1B) of lung cancer A549 cell.By the cells survival rate measuring, calculate half growth inhibitory concentration (IC
50), result is in table 1.
Oxytetracycline, the impact on lung cancer A549 cell or cervical cancer Hela cellular morphology of Propafenone and dipyrone.When working concentration is greater than the phenomenons such as the Propafenone of 0.014g/L is processed after cervical cancer Hela cell 48h, and application inverted microscope is observed, and compares with matched group, and cell quantity obviously reduces, and occurs cell rounding, broken.When phenomenons (Fig. 2) such as working concentration are respectively the oxytetracycline of 0.1,0.02, or 0.1g/L, and Propafenone and dipyrone are processed after lung cancer A549 cell 48h, compare with matched group, and cell quantity obviously reduces, and also occurs cell rounding, broken.
Oxytetracycline, the impact on lung cancer A549 cell or cervical cancer Hela cell LDH activity of Propafenone and dipyrone.Working concentration is 0.1g/L respectively, the oxytetracycline of 0.02g/L or 0.1g/L, and Propafenone and dipyrone are processed A549 cell or Hela cell 48h, and the DMSO processed group that the concentration of take is 0.1% as a control group, detects the LDH value of each experimental group and matched group.By the LDH value to each experimental group and matched group, carry out statistical analysis comparison, result shows there was no significant difference between each group, showing that these medicines suppress the propagation of these tumor cells, is not (Fig. 3) that the approach by promotion necrocytosiss such as chemical stimulations plays a role.
Oxytetracycline, the apoptosis of Propafenone and dipyrone induction lung cancer A549 cell or cervical cancer Hela cell.When working concentration is that 0.014g/L or higher Propafenone are processed after Hela cell 48h, application Hoechst 33258 detects apoptosis.Result demonstration, Propafenone can significantly promote the apoptosis (Fig. 4) of Hela cell.Illustrate that Propafenone is mainly that performance suppresses the effect of Hela cell proliferation by promoting apoptosis.When the working concentration Propafenone that is 0.014g/L, or concentration is that 0.1g/L oxytetracycline and dipyrone are processed after A549 cell 48h, and application Hoechst 33258 detects apoptosis.Result demonstration, oxytetracycline and dipyrone can both significantly promote the apoptosis of A549 cell, and Propafenone can not significantly promote the apoptosis of A549 cell.Illustrate that oxytetracycline and dipyrone are mainly that performance suppresses the effect of A549 cell proliferation by promoting apoptosis, and Propafenone not main by promoting apoptosis, but by approach performances such as retardance cell cycles, suppress the effect of A549 cell proliferation.
The present invention recognizes medical profession first, oxytetracycline, and Propafenone and dipyrone, the mode that these three kinds of medicines can both rely on concentration significantly suppresses the propagation of lung cancer A549 cell.The propagation of the remarkable cervical cancer inhibiting Hela of the mode cell that Propafenone can rely on concentration.
Useful result of the present invention is, when clinical patients with lung cancer carries out conventional antitumor drug treatment, takes oxytetracycline, and Propafenone and dipyrone can suppress the progress of tumor, the state of an illness of reduction of patient to a certain extent.When clinical Patients with Cervical Cancer carries out conventional antitumor drug treatment, take the maximum dose level that Propafenone allows, can suppress to a certain extent the progress of tumor, the state of an illness of reduction of patient.May produce very large Social benefit and economic benefit.
The present invention may impel chemist to oxytetracycline, and Propafenone and dipyrone structure are transformed, and develop more effective antitumor drug.
The present invention can make more medicine and health work person recognize, in a planned way detects the new purposes of some clinical applications, just may find more their new purposes quickly, and this is a kind of approach of effective and thrifty discovery new drug.
Accompanying drawing explanation
Fig. 1 is the impact of medicine on Hela cell and A549 cells survival rate.A: application oxytetracycline (o), Propafenone (p), dipyrone (M) or 0.1%DMSO process Hela cell 48h.Oxytetracycline (o) and dipyrone (M) working concentration are 0.2g/L.Propafenone (p) is used the variable concentrations from 0.005g/L to 0.02g/L.B: application oxytetracycline (o), Propafenone (p), dipyrone (M) or 0.1%DMSO process A549 cell 48h.Oxytetracycline (o) working concentration is respectively 0.15g/L, 0.1g/L or 0.05g/L; Propafenone (p) concentration is respectively 0.03g/L, 0.02g/L or 0.01g/L.Dipyrone (M) working concentration is respectively 0.2,0.1 or 0.05g/L.Srb assay detects cell survival rate (* p < 0.05, * * p < 0.01vs. contrast).
Table 1 is oxytetracycline, and Propafenone and dipyrone are processed respectively half growth inhibition ratio (IC after A549 cell or Hela cell 48h
50) value (g/L).
Fig. 2 is that drug treating 48h is on the impact of Hela cell and A549 cellular morphology (200 times).A-e:Hela cell; F-j:A549 cell.A and f are contrasts, and cell is processed through DMSO 0.1% (v/v).B: the concentration of oxytetracycline is 0.2g/L; C: the concentration of dipyrone is 0.2g/L; D, e: the concentration of Propafenone is 0.012 or 0.014g/L.G and h: the concentration of oxytetracycline is respectively 0.1 or 0.15g/L.I and j: the concentration of Propafenone and dipyrone is respectively 0.02 or 0.1g/L.
Fig. 3 is the impact of drug treating on Hela cell and A549 cell LDH activity.A: Propafenone (p) or 0.1%DMSO process Hela cell 48h.The working concentration of Propafenone (p) is respectively 0.012g/L or 0.014g/L.B: oxytetracycline (o), Propafenone (p), dipyrone (M) or 0.1%DMSO process A549 cell 48h.Oxytetracycline (o), Propafenone (p), the working concentration of dipyrone (M) is respectively 0.1g/L, 0.02g/L or 0.1g/L.(experiment repeats 3 times)
Fig. 4 is that drug treating is on Hela cell and the apoptotic impact of A549.A: apoptosis aspect graph; B and C: apoptosis ratio.Medicine or 0.1%DMSO process cell 48h, utilize Hoechst33258 to detect apoptosis.A:a-e:Hela cell; F-j:A549 cell.A and f are contrasts.B: oxytetracycline (o) working concentration is 0.2g/L; C: dipyrone (M) working concentration is 0.2g/L; D, e: Propafenone (p) working concentration is respectively 0.012g/L or 0.014g/L.G and h: oxytetracycline (o) working concentration is respectively 0.1g/L or 0.15g/L.I: Propafenone (p) working concentration is respectively 0.02g/L.J: dipyrone (M) working concentration is 0.1g/L.B: with the Hela apoptosis ratio that in A part, a-e is corresponding.C: with f in A part, g, the A549 apoptosis ratio that i and j are corresponding.Data from 3 different experiments (* p < 0.05).
The specific embodiment
When clinical patients with lung cancer is carried out to conventional antitumor drug treatment, take oxytetracycline, Propafenone and dipyrone, can suppress the progress of tumor, the state of an illness of reduction of patient to a certain extent.When clinical Patients with Cervical Cancer carries out conventional antitumor drug treatment, take the maximum dose level that Propafenone allows, can suppress to a certain extent the progress of tumor, the state of an illness of reduction of patient.
Claims (6)
1. finding a method for the antitumor action of non-clinical antitumor drug, is mainly to find that three kinds of non-clinical antitumor drug can significantly suppress the propagation of lung cancer A549 cell or cervical cancer Hela cell.It is characterized in that utilizing Lung Adenocarcinoma A 549 Cell and some clinical applications of cervical cancer Hela cell screening, to obtain having the non-clinical antitumor drug of antitumor action.
2. content according to claim 1, is characterized in that three kinds of non-clinical antitumor drug are oxytetracycline (oxytetracycline), Propafenone (propafenone) and dipyrone (metamizol).
3. content according to claim 1, is characterized in that oxytetracycline, and Propafenone and dipyrone can both significantly suppress the propagation of Lung Adenocarcinoma A 549 Cell; Propafenone is the propagation of cervical cancer inhibiting Hela cell significantly.
4. content according to claim 1, is characterized in that utilizing microscopic examination tumor cell form and quantity, and Preliminary screening is crossed the clinical medicine with antitumor action.
5. content according to claim 1, is characterized in that by detecting the detection of tumor cell survival rate and LDH activity, and Hoechst33258 detects apoptosis, the power of the analysis clinical medicine antitumor action of studying and preliminary mechanism.
6. content according to claim 1, is characterized in that this method utilizes Lung Adenocarcinoma A 549 Cell and cervical cancer Hela cell to screen on one's own initiative some clinical applications, rather than by clinical practice, finds passively the new purposes of old medicine.
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| CN107661324A (en) * | 2017-10-27 | 2018-02-06 | 暨南大学 | Propafenone is preparing the application in treating oesophagus cancer drug |
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