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Combined treatment with an oncolytic adenovirus and antitumor activity of vincristine against retinoblastoma cells.

Song X, Wang H, Jia R, Cun B, Zhao X, Zhou Y, Xu X, Qian G, Ge S, Fan X - Int J Mol Sci (2012)

Bottom Line: The combination therapy exerted a synergistic antitumor effect via a type of G(2)/M and S phase arrest rather than the induction of apoptosis.The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells.An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB(44) after co-treatment might be associated with cell cycle block.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; E-Mails: songxin0521@hotmail.com (X.S.); jrb6@sina.com (R.J.); catherine1_2_3@163.com (B.C.); zxp0856@sina.com (X.Z.); zhouyixiong21@gmail.com (Y.Z.); xuxu0139@hotmail.com (X.X.).

ABSTRACT
Treatment trends of retinoblastoma (RB) have gradually evolved from eye enucleation and external radiation to local treatment. Combined treatment with an oncolytic virus and chemotherapy is currently a new method in RB treatment. To investigate the therapeutic effect of oncolytic adenovirus SG600 in combination with vincristine (VCR) on retinoblastoma in vitro, the cell viability, cell cycle effects and apoptotic activity of HXO-RB(44) cells treated with SG600, VCR or SG600 plus VCR were measured using a cell counting kit-8-based procedure and flow cytometry. Western blot analysis for Akt, p-Akt, p-p53 and p-Rb protein was performed to investigate the underlying mechanisms of combined therapy. The combination therapy exerted a synergistic antitumor effect via a type of G(2)/M and S phase arrest rather than the induction of apoptosis. The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells. An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB(44) after co-treatment might be associated with cell cycle block. Western blot examination revealed that VCR might enhance SG600 replication. These results suggest that viro-chemo combination therapy is a feasible and potentially promising approach for the treatment of retinoblastoma.

No MeSH data available.


Related in: MedlinePlus

The expression patterns of Fiber, phospho-p53 and phospho-Rb in HXO-RB44 cells after different treatments for 48 h. (A) Western blot analysis of Fiber protein expression at 48 h; (B) Average band density of quantified Fiber protein after normalization to the internal control β-actin. Protein expression of Fiber in the SG600 (20 MOI) treatment group was arbitrarily set as 100; (C) western blot analysis of p-p53 and p-Rb protein expression at 48 h; (D) average band density of quantified p-p53 and p-Rb protein after normalization to the internal control β-actin. Protein expression of p-p53 and p-Rb in the NC group was arbitrarily set as 1. ** p < 0.01 relative to p-p53 and p-Rb protein expression in the SG600 or VCR (5 nM) treatment group. NC (negative control): treatment with PBS.
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f6-ijms-13-10736: The expression patterns of Fiber, phospho-p53 and phospho-Rb in HXO-RB44 cells after different treatments for 48 h. (A) Western blot analysis of Fiber protein expression at 48 h; (B) Average band density of quantified Fiber protein after normalization to the internal control β-actin. Protein expression of Fiber in the SG600 (20 MOI) treatment group was arbitrarily set as 100; (C) western blot analysis of p-p53 and p-Rb protein expression at 48 h; (D) average band density of quantified p-p53 and p-Rb protein after normalization to the internal control β-actin. Protein expression of p-p53 and p-Rb in the NC group was arbitrarily set as 1. ** p < 0.01 relative to p-p53 and p-Rb protein expression in the SG600 or VCR (5 nM) treatment group. NC (negative control): treatment with PBS.

Mentions: To evaluate whether VCR has any effect on the replication of SG600, we treated cells with SG600 (20 MOI or 50 MOI) alone, VCR (5 nM) alone, and SG600 plus VCR for 48 h, and then examined the level of adenoviral Fiber gene expression. In comparison to groups treated with SG600, the expression of Fiber in cells treated with SG600 combined with VCR was slightly increased, although it did not reach statistical significance (p > 0.05, Figure 6A,B). The results indicated that VCR might not interfere with SG600 replication.


Combined treatment with an oncolytic adenovirus and antitumor activity of vincristine against retinoblastoma cells.

Song X, Wang H, Jia R, Cun B, Zhao X, Zhou Y, Xu X, Qian G, Ge S, Fan X - Int J Mol Sci (2012)

The expression patterns of Fiber, phospho-p53 and phospho-Rb in HXO-RB44 cells after different treatments for 48 h. (A) Western blot analysis of Fiber protein expression at 48 h; (B) Average band density of quantified Fiber protein after normalization to the internal control β-actin. Protein expression of Fiber in the SG600 (20 MOI) treatment group was arbitrarily set as 100; (C) western blot analysis of p-p53 and p-Rb protein expression at 48 h; (D) average band density of quantified p-p53 and p-Rb protein after normalization to the internal control β-actin. Protein expression of p-p53 and p-Rb in the NC group was arbitrarily set as 1. ** p < 0.01 relative to p-p53 and p-Rb protein expression in the SG600 or VCR (5 nM) treatment group. NC (negative control): treatment with PBS.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472711&req=5

f6-ijms-13-10736: The expression patterns of Fiber, phospho-p53 and phospho-Rb in HXO-RB44 cells after different treatments for 48 h. (A) Western blot analysis of Fiber protein expression at 48 h; (B) Average band density of quantified Fiber protein after normalization to the internal control β-actin. Protein expression of Fiber in the SG600 (20 MOI) treatment group was arbitrarily set as 100; (C) western blot analysis of p-p53 and p-Rb protein expression at 48 h; (D) average band density of quantified p-p53 and p-Rb protein after normalization to the internal control β-actin. Protein expression of p-p53 and p-Rb in the NC group was arbitrarily set as 1. ** p < 0.01 relative to p-p53 and p-Rb protein expression in the SG600 or VCR (5 nM) treatment group. NC (negative control): treatment with PBS.
Mentions: To evaluate whether VCR has any effect on the replication of SG600, we treated cells with SG600 (20 MOI or 50 MOI) alone, VCR (5 nM) alone, and SG600 plus VCR for 48 h, and then examined the level of adenoviral Fiber gene expression. In comparison to groups treated with SG600, the expression of Fiber in cells treated with SG600 combined with VCR was slightly increased, although it did not reach statistical significance (p > 0.05, Figure 6A,B). The results indicated that VCR might not interfere with SG600 replication.

Bottom Line: The combination therapy exerted a synergistic antitumor effect via a type of G(2)/M and S phase arrest rather than the induction of apoptosis.The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells.An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB(44) after co-treatment might be associated with cell cycle block.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; E-Mails: songxin0521@hotmail.com (X.S.); jrb6@sina.com (R.J.); catherine1_2_3@163.com (B.C.); zxp0856@sina.com (X.Z.); zhouyixiong21@gmail.com (Y.Z.); xuxu0139@hotmail.com (X.X.).

ABSTRACT
Treatment trends of retinoblastoma (RB) have gradually evolved from eye enucleation and external radiation to local treatment. Combined treatment with an oncolytic virus and chemotherapy is currently a new method in RB treatment. To investigate the therapeutic effect of oncolytic adenovirus SG600 in combination with vincristine (VCR) on retinoblastoma in vitro, the cell viability, cell cycle effects and apoptotic activity of HXO-RB(44) cells treated with SG600, VCR or SG600 plus VCR were measured using a cell counting kit-8-based procedure and flow cytometry. Western blot analysis for Akt, p-Akt, p-p53 and p-Rb protein was performed to investigate the underlying mechanisms of combined therapy. The combination therapy exerted a synergistic antitumor effect via a type of G(2)/M and S phase arrest rather than the induction of apoptosis. The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells. An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB(44) after co-treatment might be associated with cell cycle block. Western blot examination revealed that VCR might enhance SG600 replication. These results suggest that viro-chemo combination therapy is a feasible and potentially promising approach for the treatment of retinoblastoma.

No MeSH data available.


Related in: MedlinePlus