CN105078996A - Pharmaceutical composition and application thereof on suppression of osteosarcoma proliferation - Google Patents
Pharmaceutical composition and application thereof on suppression of osteosarcoma proliferation Download PDFInfo
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- CN105078996A CN105078996A CN201410187199.3A CN201410187199A CN105078996A CN 105078996 A CN105078996 A CN 105078996A CN 201410187199 A CN201410187199 A CN 201410187199A CN 105078996 A CN105078996 A CN 105078996A
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Abstract
The invention discloses a pharmaceutical composition and application thereof on suppression of osteosarcoma proliferation. The pharmaceutical composition comprises pemetrexed and lobaplatin, and can suppress growth of osteosarcoma. In an animal experiment, compared with mice using normal saline, mice using the pharmaceutical composition have the characteristic that increasing of gross tumor volume of the mice is slow obviously. According to statistical analysis, the pharmaceutical composition has obvious statistical significance. According to pathological examination on the mice using the normal saline and the mice using the pharmaceutical composition, cellular degeneration necrosis of the mice using the pharmaceutical composition is obvious, and apoptosis of tumor cells can be promoted seemingly; the pharmaceutical composition can suppress proliferation of osteosarcoma cells, and can be selected by patients resisting existing first-tier osteosarcoma chemotherapeutics; and the toxicity of the pharmaceutical composition is smaller than that of the first-tier osteosarcoma chemotherapeutics.
Description
Technical field
The invention belongs to medical art, relate to a kind of pharmaceutical composition and application thereof, particularly a kind of pharmaceutical composition and the application in suppression osteosarcoma propagation thereof.
Background technology
Osteosarcoma is apt to occur in teenager, originate from mesenchymal tissue, with the malignant tumor that fusiformis tumor cell is feature, principal pathogenetic position is positioned at the metaphysis of distal femur, proximal tibia, main clinical manifestation is local pain and swelling, hypnalgia is the large feature of one, and occasionally have generation pathologisch Bruch, x-ray shows as pathological changes bone metaphysis skeletonization and osteolytic is damaged and deposits.Therapeutic scheme conventional is at present that new adjuvant chemotherapy is in conjunction with ocal resection.Medicine the most frequently used in current osteosarcoma chemotherapy is epirubicin, high-dose methotrexate, cisplatin and ifosfamide, and the chemotherapy regimen of domestic application is many carries out adjustment application according to many clinical treatment of osteosarcoma center complex suggested designs.And in conjunction with preoperative neoadjuvant chemotherapy, the development of the progress of muscle skeleton imaging, artificial prosthesis design and surgical technic, increasing patient has possessed the condition of limb-sparing surgery, and the storage rate of limbs reaches more than 80%.For the patient that osteosarcoma with lung transfer occurs, prognosis is then general not good, and the overall survival of current this kind of patient is not about 0% ~ 50% not etc.For improving the survival rate of this kind of patient, many scholars just carry out all kinds of research and clinical observation to this field, attempt giving chemotherapy regimen or and the targeted therapy that this kind of patient uses individuation simultaneously.
Pemetrexed is the anti-folic acid metabolism class medicine based on the Mutiple Targets of new generation that traditional antimetabolite methotrexate and fluorouracil basis are developed, and has the model of action similar with methotrexate, and wider than the sphere of action of methotrexate.Current pemetrexed has been approved for the first-line treatment of malignant pleural mesothelioma and the second line treatment of nonsmall-cell lung cancer, and it has comparatively clear and definite anti-tumor effect to multiple solid tumor.Lobaplatin (LBP) is platinum antineoplastic medicine of new generation, and research shows that its antitumous effect and DDP are quite even better, but nephrotoxicity, nervous system and digestive tract reaction are all less than DDP, and without the need to aquation.
Summary of the invention
Technical problem solved by the invention is provide a kind of pharmaceutical composition and suppressing the application in osteosarcoma propagation.
The technical solution realizing the object of the invention is: a kind of pharmaceutical composition, and described compositions is made up of pemetrexed and lobaplatin.
The dosage of described pemetrexed is 5mg/kg, and the dosage of lobaplatin is 3mg/kg.
Aforementioned pharmaceutical compositions is suppressing the application in osteosarcoma propagation.
Described osteosarcoma causes at the human osteosarcoma cell line 143-B-RFP of the intra-bone marrow injection red fluorescent protein transfection of nude mice femur.
Described pharmaceutical composition, suppressing the application of osteosarcoma propagation, comprises the mammal of people.
Compared with prior art, its remarkable advantage is in the present invention:
1. pharmaceutical composition of the present invention, be now applied to other malignant tumor chemotherapy, its Drug safety has clinical guarantee.
2. pharmaceutical composition of the present invention can suppress osteosarcomatous growth, in zoopery, compared with use normal saline group nude mice, uses the experimental group nude mouse tumor volume of this compositions to increase obviously slowly, and through statistical analysis, has obvious statistical significance.
3. the present invention carries out pathological examination to two groups of Osteosarcoma in Nude Mice tumors, and use the experimental group nude mouse tumor wall regeneration of this compositions obvious, surface energy impels the apoptosis of tumor cell.
4. pharmaceutical composition of the present invention can suppress the propagation of osteosarcoma cell, can be used as the selection to a current line osteosarcoma chemotherapeutics drug resistance patient, and has the toxic reaction more slight than a line osteosarcoma chemotherapeutics.
Accompanying drawing explanation
Fig. 1 is G1 group of the present invention and G2 group nude mouse tumor change in volume figure.
Fig. 2 is G1 group of the present invention experiment starting point nude mice fluorescence imaging figure.
Fig. 3 is G2 group of the present invention experiment starting point nude mice fluorescence imaging figure.
Fig. 4 is G1 group experimental endpoints nude mice fluorescence imaging figure of the present invention.
Fig. 5 is G2 group experimental endpoints nude mice fluorescence imaging figure of the present invention.
Fig. 6 is G1 group tumor cell morphology of the present invention.
Fig. 7 is G2 group tumor cell morphology of the present invention.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1 animal model
Laboratory animal is the male nude mouse in 4-6 week.Raise under standard laboratory conditions: 12 h light-12 h dark cycle, freely absorb water and food.Human osteosarcoma cell line 143-B-RFP 37 DEG C, 5%CO in RPMI-1640 of red fluorescent protein transfection
2cultivate under saturated humidity condition.By tumor cell injection in the medullary cavity of nude mice femur, often only inoculate 2x10
6cell.Whole operating process completes in superclean bench.After completing orthotopic transplantation, the health status of mice and the growing state of tumor are monitored.After treating that whole mouse tumor grows, it is divided into 2 groups by gross tumor volume according to animal at random, and first group (G1) is matched group (Saline), gives corresponding drug media (normal saline) process in experimentation; Second group (G2) adds lobaplatin group (pemetrexed adds lobaplatin) for pemetrexed, and intraperitoneal injection pemetrexed adds lobaplatin.
Embodiment 1: coupling pemetrexed adds the inhibitory action research of lobaplatin to Osteosarcoma in Nude Mice
1. weighing body weight: weigh 1-2 time and record to weekly experiment nude mice.
2. tumor size kind of calliper: 1-2 time weekly; Gross tumor volume is gone out: gross tumor volume (mm3)=1/2ab according to following formulae discovery
2, a is tumor major diameter, and b is tumor minor axis.
3. integral fluorescence Imaging Study: the tumor in situ size measuring weekly 1-2 mice under fluoroscopic image system, measure tumor major diameter, minor axis and imagery coverage, calculate the volume of tumor with Image-Pro, and under fluoroscopic image system, take representative fluoroscopic image photo in weekly; Extremely experiment 4th week is experimental endpoints.
4. data analysis: the comparison ANOVA statistical method between many groups carries out statistical analysis, P < 0.05 has been considered to significance difference.
Table 1: each group mean tumour volume measurement result (volume unit mm3) in experimentation
Table 2: respectively organize nude mouse tumor volume during experimental endpoints
G1(mm3) | G2(mm3) |
3588.4 | 1397.3 |
1414.3 | 933.4 |
3274.3 | 1286.1 |
3159.0 | 1511.9 |
5418.1 | 2281.8 |
Table 3: experimental endpoints two groups of gross tumor volume statistical analysis
Group | P value |
G1 and G2 | 0.02 |
In experimentation, each group mean tumour volume measurement result is in table 1, nude mouse tumor volume is respectively organized in table 2 during terminal, experimental endpoints two groups of gross tumor volume statistical analysis are in table 3, G1 group and G2 group nude mouse tumor change in volume are shown in Fig. 1, experiment starting point nude mice fluorescence imaging figure is shown in Fig. 2 and 3 respectively, experimental endpoints nude mice fluorescence imaging figure is shown in Figure 4 and 5 respectively, from table 1-3 and Fig. 1-5, coupling pemetrexed adds lobaplatin (G2 group) compared with normal saline (G1 group), significantly can suppress the growth of Osteosarcoma in Nude Mice gross tumor volume, comprise and regularly tumor photofulorography is carried out to two groups of nude mices from experimental session and measure tumor calculate volume, and the gross tumor volume that experimental endpoints is surveyed.And using T inspection to carry out statistical analysis to two groups of gross tumor volumes of experimental endpoints, conclusion is for compared with G1 group, and G2 group increases Tumor suppression volume statistical significance.
Embodiment 2: pemetrexed adds the morphocytology research that lobaplatin suppresses Osteosarcoma in Nude Mice
During experimental endpoints, put to death nude mice, each group of nude mouse tumor tissue is taken out, make the pathological section HE that walks abreast and dye, observe each group of tumor tissues morphological change under the microscope, see Fig. 6 and Fig. 7.Visible G1 group tumor tissues fills the air distribution, oncocyte similar round, fusiformis, core similar round, and engrain, has atypia, the red dye of endochylema.Regional area is downright bad as seen.G2 group tumor tissues subregion is large stretch of downright bad, oncocyte degeneration, nuclear hyperchromatism, the red dye of endochylema, part endochylema vacuolar degeneration.Experiment conclusion proves that pemetrexed adds lobaplatin and can obviously suppress Osteosarcoma in Nude Mice cell proliferation, and can make tumor cell necrosis.
Claims (6)
1. a pharmaceutical composition, is characterized in that, described compositions comprises pemetrexed and lobaplatin.
2. pharmaceutical composition as claimed in claim 1, it is characterized in that, the dosage of described pemetrexed is 5mg/kg.
3. pharmaceutical composition as claimed in claim 1, it is characterized in that, the dosage of lobaplatin is 3mg/kg.
4. pharmaceutical composition as claimed in claim 1 is suppressing the application in osteosarcoma propagation.
5. apply as claimed in claim 4, it is characterized in that, described osteosarcoma causes at the human osteosarcoma cell line 143-B-RFP of the intra-bone marrow injection red fluorescent protein transfection of nude mice femur.
6. apply as claimed in claim 4, it is characterized in that, described application comprises the mammal of people.
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN1857208A (en) * | 2006-03-17 | 2006-11-08 | 山东蓝金生物工程有限公司 | Slow released anticancer injection with both antimetabolite and its synergist |
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CN1857208A (en) * | 2006-03-17 | 2006-11-08 | 山东蓝金生物工程有限公司 | Slow released anticancer injection with both antimetabolite and its synergist |
Non-Patent Citations (5)
Title |
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刘德林等: "培美曲塞联合洛铂治疗多线化疗失败的晚期乳腺癌临床观察", 《江苏医药》 * |
包明红等: "培美曲塞联合洛铂治疗肺腺癌的近期疗效和安全性研究", 《中华肿瘤防治杂志》 * |
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