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Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

Bassiony H, Sabet S, Salah El-Din TA, Mohamed MM, El-Ghor AA - PLoS ONE (2014)

Bottom Line: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor.A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor.It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.

ABSTRACT

Background: Magnetite nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues.

Method: MNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry.

Results: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group.

Conclusion: MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

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Related in: MedlinePlus

Comparison of effect of MNPs on the expression of p53 and p16 mRNA in ESC and skeletal muscles in our different six groups of mice.(A) Semiquantitative RT-PCR to amplify p53 (left), p16 (right) and GAPDH genes. Representative images are shown. (B) Real time PCR was performed to amplify p53 (left), p16 (right) and GAPDH genes. The mRNA ratios of p53 and p16 to GAPDH were calculated using the ΔΔCt method. Each bar represents mean ± SE of six independent experiment. Asterisks indicate statistically significant differences between this group and the control group (p<0.05). Both methods show that MNPs increases the expression level of p53 and p16 mRNA in Ehrlich tumor treated IP (group 5) and IT (group 6). Primers described in Table 1. - The same letter means that there is no significant difference between the two groups by using Duncan multiple comparison test (P>0.05). - The different letters means that there is a significant difference between the two groups by using Duncan multiple comparison test (P<0.05). - Asterisks indicate statistically significant compared with negative control using student t- test.
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pone-0111960-g008: Comparison of effect of MNPs on the expression of p53 and p16 mRNA in ESC and skeletal muscles in our different six groups of mice.(A) Semiquantitative RT-PCR to amplify p53 (left), p16 (right) and GAPDH genes. Representative images are shown. (B) Real time PCR was performed to amplify p53 (left), p16 (right) and GAPDH genes. The mRNA ratios of p53 and p16 to GAPDH were calculated using the ΔΔCt method. Each bar represents mean ± SE of six independent experiment. Asterisks indicate statistically significant differences between this group and the control group (p<0.05). Both methods show that MNPs increases the expression level of p53 and p16 mRNA in Ehrlich tumor treated IP (group 5) and IT (group 6). Primers described in Table 1. - The same letter means that there is no significant difference between the two groups by using Duncan multiple comparison test (P>0.05). - The different letters means that there is a significant difference between the two groups by using Duncan multiple comparison test (P<0.05). - Asterisks indicate statistically significant compared with negative control using student t- test.

Mentions: Changes of the gene expressions by MNPs were shown in Figure 8. We examined the expression of p53 and p16 genes at the mRNA level by conventional semiquantitative RT-PCR (Fig. 8A) and results were confirmed by real time PCR (Fig. 8B). Results showed that the expression levels of p53 and p16 were significantly (p<0.05) down-regulated in untreated ESC (group 4) compared with control muscles (group 1). Furthermore, the levels of p53 and p16 expression were significantly increased (p<0.05) in ESC treated IT with MNPs (group 6) when compared with ESC group and reached nearly the expression level in the control. In addition; significant increase in expression of p53 and p16 was noticed in ESC treated IP (group 5) when compared with ESC group, however, this increase still significantly less than the control level.


Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

Bassiony H, Sabet S, Salah El-Din TA, Mohamed MM, El-Ghor AA - PLoS ONE (2014)

Comparison of effect of MNPs on the expression of p53 and p16 mRNA in ESC and skeletal muscles in our different six groups of mice.(A) Semiquantitative RT-PCR to amplify p53 (left), p16 (right) and GAPDH genes. Representative images are shown. (B) Real time PCR was performed to amplify p53 (left), p16 (right) and GAPDH genes. The mRNA ratios of p53 and p16 to GAPDH were calculated using the ΔΔCt method. Each bar represents mean ± SE of six independent experiment. Asterisks indicate statistically significant differences between this group and the control group (p<0.05). Both methods show that MNPs increases the expression level of p53 and p16 mRNA in Ehrlich tumor treated IP (group 5) and IT (group 6). Primers described in Table 1. - The same letter means that there is no significant difference between the two groups by using Duncan multiple comparison test (P>0.05). - The different letters means that there is a significant difference between the two groups by using Duncan multiple comparison test (P<0.05). - Asterisks indicate statistically significant compared with negative control using student t- test.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4222961&req=5

pone-0111960-g008: Comparison of effect of MNPs on the expression of p53 and p16 mRNA in ESC and skeletal muscles in our different six groups of mice.(A) Semiquantitative RT-PCR to amplify p53 (left), p16 (right) and GAPDH genes. Representative images are shown. (B) Real time PCR was performed to amplify p53 (left), p16 (right) and GAPDH genes. The mRNA ratios of p53 and p16 to GAPDH were calculated using the ΔΔCt method. Each bar represents mean ± SE of six independent experiment. Asterisks indicate statistically significant differences between this group and the control group (p<0.05). Both methods show that MNPs increases the expression level of p53 and p16 mRNA in Ehrlich tumor treated IP (group 5) and IT (group 6). Primers described in Table 1. - The same letter means that there is no significant difference between the two groups by using Duncan multiple comparison test (P>0.05). - The different letters means that there is a significant difference between the two groups by using Duncan multiple comparison test (P<0.05). - Asterisks indicate statistically significant compared with negative control using student t- test.
Mentions: Changes of the gene expressions by MNPs were shown in Figure 8. We examined the expression of p53 and p16 genes at the mRNA level by conventional semiquantitative RT-PCR (Fig. 8A) and results were confirmed by real time PCR (Fig. 8B). Results showed that the expression levels of p53 and p16 were significantly (p<0.05) down-regulated in untreated ESC (group 4) compared with control muscles (group 1). Furthermore, the levels of p53 and p16 expression were significantly increased (p<0.05) in ESC treated IT with MNPs (group 6) when compared with ESC group and reached nearly the expression level in the control. In addition; significant increase in expression of p53 and p16 was noticed in ESC treated IP (group 5) when compared with ESC group, however, this increase still significantly less than the control level.

Bottom Line: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor.A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor.It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.

ABSTRACT

Background: Magnetite nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues.

Method: MNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry.

Results: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group.

Conclusion: MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

Show MeSH
Related in: MedlinePlus