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Bidirectional regulation of angiogenesis and miR-18a expression by PNS in the mouse model of tumor complicated by myocardial ischemia.

Yang Q, Wang X, Cui J, Wang P, Xiong M, Jia C, Liu L, Ning B, Li L, Wang W, Chen Y, Zhang T - BMC Complement Altern Med (2014)

Bottom Line: PNS treatment led to decreased expression of CD34 and vWF in tumor and increased expression of these vascular markers in heart.PNS treatment resulted in reduced expression of miR-18a in tumor and upregulated expression of miR-18a in heart.Our data demonstrated for the first time that PNS exerts tissue specific regulatory effects on angiogenesis in part through modulating the expression of miR-18a, which could be responsible for its bidirectional effect on complex disease conditions where paradoxical angiogenesis is implicated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Yueyang Hospital, Shanghai University of TCM, 110 Ganhe Rd, Shanghai 200437, China. chenyu6639@gmail.com.

ABSTRACT

Background: Panax Notoginseng Saponins (PNS) is the major class of active constituents of notoginseng, a natural product extensively used as a therapeutic agent in China. Tumor when accompanied by cardiovascular disorders poses a greater challenge for clinical management given the paradoxical involvement of angiogenesis, therefore gaining increased research attention. This study aim to investigate effects of PNS and its activity components in the mouse model of tumor complicated with myocardial ischemia.

Methods: Tumor complexed with myocardial ischemia mouse model was first established, which was followed by histological and immunohistochemistry examination to assess the effect of indicated treatments on tumor, myocardial ischemia and tissue specific angiogenesis. MicroRNA (miRNA) profiling was further carried out to identify potential miRNA regulators that might mechanistically underline the therapeutic effects of PNS in this complex model.

Results: PNS and its major activity components Rg1, Rb1 and R1 suppressed tumor growth and simultaneously attenuated myocardial ischemia. PNS treatment led to decreased expression of CD34 and vWF in tumor and increased expression of these vascular markers in heart. PNS treatment resulted in reduced expression of miR-18a in tumor and upregulated expression of miR-18a in heart.

Conclusions: Our data demonstrated for the first time that PNS exerts tissue specific regulatory effects on angiogenesis in part through modulating the expression of miR-18a, which could be responsible for its bidirectional effect on complex disease conditions where paradoxical angiogenesis is implicated. Therefore, our study provides experimental evidence warranting evaluation of PNS and related bioactive component as a rational therapy for complex disease conditions including co-manifestation of cancer and ischemic cardiovascular disease.

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PNS or its major active components Rg1, Rb1, and R1 inhibited tumor growth in the complex mouse model. A. Growth curve of the tumor from vehicle-treated complex model (model), and PNS (150 mg/kg), Rg1 (50 mg/kg), Rb1 (50 mg/kg), R1 (10 mg/kg) treatment, respectively. Tumor volume (TV) (mm3) = (width2 × length)/2. B. Size of dissected tumor at the termination of experiment.
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Figure 1: PNS or its major active components Rg1, Rb1, and R1 inhibited tumor growth in the complex mouse model. A. Growth curve of the tumor from vehicle-treated complex model (model), and PNS (150 mg/kg), Rg1 (50 mg/kg), Rb1 (50 mg/kg), R1 (10 mg/kg) treatment, respectively. Tumor volume (TV) (mm3) = (width2 × length)/2. B. Size of dissected tumor at the termination of experiment.

Mentions: The complex mouse model was established by inoculating C57BL/6J mouse with LLC cells followed by isoproterenol (ISO) administration at the dose of 10 mg/kg BW for 10 days to induce myocardial ischemic injuries. ISO is a sympathomimetic β-adrenergic receptor agonist and induces infarct like cell death of cardiac muscle. The animal model of ISO-induced myocardial injury recapitulates metabolic and morphological changes occurring during human myocardial infarction, therefore, it is frequently adopted as a standardized model for evaluating the cardiac protective effects of pharmacological agents against myocardial ischemic injury [15-19]. Tumor growth of the complex mice treated with PBS vehicle or indicated treatments including PNS, Rg1, Rb1 or R1 were monitored and documented. As shown in Figure 1, tumor volume was progressively increased in the vehicle-treated complex mice. PNS, Rg1, or R1 treatment exhibited more significant effects on inhibiting tumor growth than that observed from Rb1 treatment. The tumor inhibition rates (Table 1) revealed a marked effect of PNS, Rg1, Rb1, or R1 on inhibiting tumor growth in the complex model. Note that among all the compounds examined, PNS showed the most pronounced effect on tumor inhibition in this complex mouse model.


Bidirectional regulation of angiogenesis and miR-18a expression by PNS in the mouse model of tumor complicated by myocardial ischemia.

Yang Q, Wang X, Cui J, Wang P, Xiong M, Jia C, Liu L, Ning B, Li L, Wang W, Chen Y, Zhang T - BMC Complement Altern Med (2014)

PNS or its major active components Rg1, Rb1, and R1 inhibited tumor growth in the complex mouse model. A. Growth curve of the tumor from vehicle-treated complex model (model), and PNS (150 mg/kg), Rg1 (50 mg/kg), Rb1 (50 mg/kg), R1 (10 mg/kg) treatment, respectively. Tumor volume (TV) (mm3) = (width2 × length)/2. B. Size of dissected tumor at the termination of experiment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4060854&req=5

Figure 1: PNS or its major active components Rg1, Rb1, and R1 inhibited tumor growth in the complex mouse model. A. Growth curve of the tumor from vehicle-treated complex model (model), and PNS (150 mg/kg), Rg1 (50 mg/kg), Rb1 (50 mg/kg), R1 (10 mg/kg) treatment, respectively. Tumor volume (TV) (mm3) = (width2 × length)/2. B. Size of dissected tumor at the termination of experiment.
Mentions: The complex mouse model was established by inoculating C57BL/6J mouse with LLC cells followed by isoproterenol (ISO) administration at the dose of 10 mg/kg BW for 10 days to induce myocardial ischemic injuries. ISO is a sympathomimetic β-adrenergic receptor agonist and induces infarct like cell death of cardiac muscle. The animal model of ISO-induced myocardial injury recapitulates metabolic and morphological changes occurring during human myocardial infarction, therefore, it is frequently adopted as a standardized model for evaluating the cardiac protective effects of pharmacological agents against myocardial ischemic injury [15-19]. Tumor growth of the complex mice treated with PBS vehicle or indicated treatments including PNS, Rg1, Rb1 or R1 were monitored and documented. As shown in Figure 1, tumor volume was progressively increased in the vehicle-treated complex mice. PNS, Rg1, or R1 treatment exhibited more significant effects on inhibiting tumor growth than that observed from Rb1 treatment. The tumor inhibition rates (Table 1) revealed a marked effect of PNS, Rg1, Rb1, or R1 on inhibiting tumor growth in the complex model. Note that among all the compounds examined, PNS showed the most pronounced effect on tumor inhibition in this complex mouse model.

Bottom Line: PNS treatment led to decreased expression of CD34 and vWF in tumor and increased expression of these vascular markers in heart.PNS treatment resulted in reduced expression of miR-18a in tumor and upregulated expression of miR-18a in heart.Our data demonstrated for the first time that PNS exerts tissue specific regulatory effects on angiogenesis in part through modulating the expression of miR-18a, which could be responsible for its bidirectional effect on complex disease conditions where paradoxical angiogenesis is implicated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Yueyang Hospital, Shanghai University of TCM, 110 Ganhe Rd, Shanghai 200437, China. chenyu6639@gmail.com.

ABSTRACT

Background: Panax Notoginseng Saponins (PNS) is the major class of active constituents of notoginseng, a natural product extensively used as a therapeutic agent in China. Tumor when accompanied by cardiovascular disorders poses a greater challenge for clinical management given the paradoxical involvement of angiogenesis, therefore gaining increased research attention. This study aim to investigate effects of PNS and its activity components in the mouse model of tumor complicated with myocardial ischemia.

Methods: Tumor complexed with myocardial ischemia mouse model was first established, which was followed by histological and immunohistochemistry examination to assess the effect of indicated treatments on tumor, myocardial ischemia and tissue specific angiogenesis. MicroRNA (miRNA) profiling was further carried out to identify potential miRNA regulators that might mechanistically underline the therapeutic effects of PNS in this complex model.

Results: PNS and its major activity components Rg1, Rb1 and R1 suppressed tumor growth and simultaneously attenuated myocardial ischemia. PNS treatment led to decreased expression of CD34 and vWF in tumor and increased expression of these vascular markers in heart. PNS treatment resulted in reduced expression of miR-18a in tumor and upregulated expression of miR-18a in heart.

Conclusions: Our data demonstrated for the first time that PNS exerts tissue specific regulatory effects on angiogenesis in part through modulating the expression of miR-18a, which could be responsible for its bidirectional effect on complex disease conditions where paradoxical angiogenesis is implicated. Therefore, our study provides experimental evidence warranting evaluation of PNS and related bioactive component as a rational therapy for complex disease conditions including co-manifestation of cancer and ischemic cardiovascular disease.

Show MeSH
Related in: MedlinePlus