CN105078972A - Composition and application thereof on suppression of osteosarcoma proliferation - Google Patents
Composition and application thereof on suppression of osteosarcoma proliferation Download PDFInfo
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- CN105078972A CN105078972A CN201410187437.0A CN201410187437A CN105078972A CN 105078972 A CN105078972 A CN 105078972A CN 201410187437 A CN201410187437 A CN 201410187437A CN 105078972 A CN105078972 A CN 105078972A
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Abstract
The invention discloses a composition and application thereof on suppression of osteosarcoma proliferation. The composition comprises sunitinib and lobaplatin, and can suppress growth of osteosarcoma. In an animal experiment, compared with mice using normal saline, mice using the composition have the characteristic that increasing of gross tumor volume of the mice is slow obviously. According to statistical analysis, the composition has obvious statistical significance. According to pathological examination on the mice using the normal saline and the mice using the composition, cellular degeneration necrosis of the mice using the composition is obvious, and apoptosis of tumor cells can be promoted seemingly; the composition can suppress proliferation of osteosarcoma cells, and can be selected by patients resisting existing first-tier osteosarcoma chemotherapeutics; and the toxicity of the 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 compositions and application thereof, particularly the application of a kind of compositions and suppression osteosarcoma propagation aspect 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.
Sutent is one of anti-tumor drugs targeting that known at present action target spot is maximum, has the anti-tumor activity of wide spectrum.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
The object of the present invention is to provide the application of a kind of compositions and suppression osteosarcoma propagation aspect thereof.
The technical solution realizing the object of the invention is: a kind of compositions, and described compositions is made up of Sutent and lobaplatin.
The dosage of described Sutent is 40mg/kg, and the dosage of lobaplatin is 3mg/kg.
Above-mentioned composition 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 compositions, suppressing the application in osteosarcoma propagation, comprises the mammal of people.
Compared with prior art, its remarkable advantage is in the present invention:
1. compositions of the present invention, be now applied to other malignant tumor chemotherapy, its Drug safety has clinical guarantee.
2. compositions 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. compositions 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 and accompanying drawing, the present invention is described in further detail.
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 (coupling Sutent adds lobaplatin) for Sutent, and Sutent administering mode is gavage, and lobaplatin is intraperitoneal injection.
Embodiment 1: coupling Sutent 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; Causing 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 mm in experimentation
3)
Table 2: respectively organize nude mouse tumor volume during experimental endpoints
| G1(mm3) | G2(mm3) |
| 3588.4 | 1932.6 |
| 1414.3 | 948.9 |
| 3274.3 | 839.2 |
| 3159.0 | 889.0 |
| 5418.1 | 1367.5 |
Table 3: experimental endpoints two groups of gross tumor volume statistical analysis
| Group | P value |
| G1 and G2 | 0.01 |
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 Sutent 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: coupling Sutent 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 major part is downright bad, the residual obvious degeneration of tumor cell, nuclear hyperchromatism, the red dye of endochylema, part endochylema vacuolar degeneration.Experiment conclusion proves that Sutent adds lobaplatin and can obviously suppress Osteosarcoma in Nude Mice cell proliferation, and can make tumor cell necrosis.
Claims (6)
1. a compositions, is characterized in that described compositions comprises Sutent and lobaplatin.
2. compositions according to claim 1, is characterized in that the dosage of described Sutent is 40mg/kg.
3. compositions according to claim 1, is characterized in that the dosage of described lobaplatin is 3mg/kg.
4. compositions as claimed in claim 1 is suppressing the application in osteosarcoma propagation.
5. application according to claim 4, 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. application according to claim 4, is characterized in that, described application comprises the mammal of people.
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| CN201410187437.0A CN105078972A (en) | 2014-05-05 | 2014-05-05 | Composition and application thereof on suppression of osteosarcoma proliferation |
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| CN201410187437.0A CN105078972A (en) | 2014-05-05 | 2014-05-05 | Composition and application thereof on suppression of osteosarcoma proliferation |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081206A (en) * | 2007-06-29 | 2007-12-05 | 济南康泉医药科技有限公司 | Anti-cancer medicine composition containing tyrosine kinase restraining agent |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081206A (en) * | 2007-06-29 | 2007-12-05 | 济南康泉医药科技有限公司 | Anti-cancer medicine composition containing tyrosine kinase restraining agent |
Non-Patent Citations (2)
| Title |
|---|
| JOHN M. MARIS, ET AL.: "Initial Testing (Stage 1) of Sunitinib by the Pediatric Preclinical Testing Program", 《PEDIATR BLOOD CANCER》 * |
| 朱皓东等: "含洛铂方案的新辅助化疗在骨肉瘤及尤因肉瘤中的疗效观察", 《中国骨与关节外科》 * |
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