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Experimental Study of Endostar Injection Concomitant with Cryoablation on Lung Adenocarcinoma A549 Xenografts

  • Ma, Chun-Hua (Department of Intervention, Tianjin Huanhu Hospital, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory) ;
  • Jiang, Rong (Department of Intervention, Tianjin Huanhu Hospital, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory) ;
  • Li, Jin-Duo (Department of Intervention, Tianjin Huanhu Hospital, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory) ;
  • Wang, Bin (Department of Intervention, Tianjin Huanhu Hospital, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory) ;
  • Sun, Li-Wei (Department of Intervention, Tianjin Huanhu Hospital, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory) ;
  • Lv, Yuan (Department of Intervention, Tianjin Huanhu Hospital, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory)
  • Published : 2013.11.30

Abstract

Objective: To explore the inhibiting effect and mechanism of Endostar injection concomitant with cryoablation on lung adenocarcinoma A549 xenografts in nude mice. Materials and Methods: A total of 24 nude mice with subcutaneous xenografts of the A549 cell line were established and divided into 4 groups when the maximal diameters of tumors became 1 cm: control group, Endostar group, cryoablation group and combination group (Endostar concomitant with cryoablation). The nude mice were sacrificed after 21-days treatment, tumour tissues were removed to measure their volume, in situ test of TdT-mediated dUTP nick end labeling (TUNEL) was adopted to determine the cellular apoptosis around freezing injury zones, and immunohistochemical SP test was applied for the detection of micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression levels. Results: At 21-days after treatment, the growth velocities of control group, Endostar group, cryoablation group and combination group were $236.7{\pm}51.2%$, $220.0{\pm}30.6%$, $159.5{\pm}29.3%$ and $103.3{\pm}25.5%$ (P<0.01), while cellular apoptosis rates of tumors were $21.7{\pm}2.34%$, ($22.17{\pm}1.47$)%, $38.3{\pm}1.37%$ and $49.2{\pm}1.72%$, (P<0.01), respectively, according to the immunohistochemical test. MVD and VEGF expression levels in the combination group were both lower than in other groups (P<0.01), also being positively related (r=0.925, P<0.01). Conclusions: Endostar can significantly improve the inhibitory effects of cryoablation on xenografts of lung adenocarcinoma A549, and the mechanism is probably associated with its function as an inhibitor of tumour neo-angiogenesis through down-regulating VEGF expression.

Keywords

References

  1. Fei ZH, Yao CY, Yang XL, et al (2013). Serum BMP-2 Up-regulation as an Indicator of Poor Survival in Advanced Non-small Cell Lung Cancer Patients. Asian Pac J Cancer Prev, 14, 5293-9. https://doi.org/10.7314/APJCP.2013.14.9.5293
  2. Folkman J (2006). Antiangiogenesis in cancer therapy-endostatin and its mechamisms of action. Exp Cell Res, 312, 594-607. https://doi.org/10.1016/j.yexcr.2005.11.015
  3. Gary Onik (2008). Rationale for a "Male Lumpectomy" a Prostate Cancer targeted approach using cryoablation: results in 21 patients with at Least 2 years of follow-up. Cardiovasc Intervent Radiol, 31, 98-106. https://doi.org/10.1007/s00270-004-0232-0
  4. Guo Z, Wang HT, Xing WG, et al (2010). A preliminary clinical study of targeted cryoablation of prostate in the treatment of T3N0M0 prostate cancer. National Med J Chin, 90, 2815-9.
  5. Hu KW, Li QW, Zuo MH, et al (2007). Clinical observation on the combined treatment of 57 cases of non-small cell lung cancer using argon-helium cryosurgery and Chinese herbal medicine. Chin J Integr Med, 13, 224-7. https://doi.org/10.1007/s11655-007-0224-4
  6. Kimura M, Rabbani Z, Mouraviev V, et al (2010). Morphology of hypoxia following cryoablation in a prostate cancer murine model: its relationship to necrosis, apoptosis and, microvessel density. Cryobiology, 61, 148-54. https://doi.org/10.1016/j.cryobiol.2010.06.010
  7. Lee CG, Heijn M, di Tomaso E, et al (2000). Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res, 60, 5565-70.
  8. Liu YC, Zhou SB, Gao F, et al (2013).Chemotherapy and late course three dimensional conformal radiotherapy for treatment of patients with stage III non- small cell lung cancer. Asian Pac J Cancer Prev, 14, 2663-5. https://doi.org/10.7314/APJCP.2013.14.4.2663
  9. Lu YY, Huang XE, Xu L, et al (2013). Potential predictors of sensitivity to pemetrexed as first-line chemotherapy for patients with advanced non-squamous NSCLCs. Asian Pac J Cancer Prev, 14, 2005-8. https://doi.org/10.7314/APJCP.2013.14.3.2005
  10. Mauceri HJ, Hanna NN, Beckett MA, et al (1998). Combined effects of angiostatin and ionizing radiation in antitumourtherapy. Nature, 394, 287- 91. https://doi.org/10.1038/28412
  11. Ueda M,Terai Y,Kurnagai K, et a1 (1999).Correlation between tumor angiogenesis and expression of thymidine phosphorylase, and patient outcome in uterine cervical carcinoma. Hum Pathol, 30, 1389-94. https://doi.org/10.1016/S0046-8177(99)90074-6
  12. Wang JW, Sun Y, Liu YY, et al (2005). A random, double-blind, control, multi-center phase III clinical study of Endostatin concomitant with NP protocol on advanced NSCLC. Chin J Lung Cancer, 48, 283-90.
  13. Xing WG, Guo Z, Wang HT, et al (2008). Percutaneous cryoablation of prostate cancer guided by rectal ultrasound: a retrospective analysis of 42 cases. Chin J Radio, 42, 807-11.
  14. Yan HA, Shen K, Huang XE (2013). Clinical study on mannan peptide combined with TP regimen in treating patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4801-4. https://doi.org/10.7314/APJCP.2013.14.8.4801
  15. Yin HT, Tian QZ, Guan L (2013). In vitro and in vivo evaluation of the antitumor efficiency of resveratrol against lung cancer. Asian Pac J Cancer Prev, 14, 1703-6. https://doi.org/10.7314/APJCP.2013.14.3.1703

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