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sCLU regulates cisplatin chemosensitivity of lung cancer cells in vivo.

Ma G, Cai H, Gao L, Wang M, Wang H - World J Surg Oncol (2015)

Bottom Line: The effect of sCLU silencing or overexpression on pAkt and pERK1/2 expression and chemosensitivity in vivo was detected by Western blot assay.The results showed sCLU silencing increased the chemosensitivity of A549(DDP) cells to DDP in vivo via downregulation of pAkt and pERK1/2 expression.And sCLU overexpression decreased the chemosensitivity of A549 cells to DDP in vivo via upregulation of pAkt and pERK1/2 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Lab, People's Hospital of Laiwu, Laiwu, China. maguoliang7782@sina.com.

ABSTRACT

Background: In a previous analysis using a lung cancer cell line model, we have found that therapies directed against secreted clusterin (sCLU) and its downstream signaling targets pAkt and pERK1/2 may have the potential to enhance the efficacy of cisplatin (DDP)-based chemotherapy in vitro. Here, we investigated the therapies directed against sCLU on the DDP-based chemotherapy in vivo and explored the mechanism.

Methods: Using lung cancer cell lines, A549 cells and DDP-resistant A549 cells (A549(DDP)), we determined the effect of sCLU silencing using short interfering double-stranded RNA (siRNA) on chemosensitivity in immunocompromised mice bearing A549(DDP) tumors. We then determined the effect of sCLU overexpression via stable sCLU transfection on chemosensitivity in immunocompromised mice bearing A549 tumors. The effect of sCLU silencing or overexpression on pAkt and pERK1/2 expression and chemosensitivity in vivo was detected by Western blot assay.

Results: The results showed sCLU silencing increased the chemosensitivity of A549(DDP) cells to DDP in vivo via downregulation of pAkt and pERK1/2 expression. And sCLU overexpression decreased the chemosensitivity of A549 cells to DDP in vivo via upregulation of pAkt and pERK1/2 expression.

Conclusions: We therefore concluded that the DDP-induced sCLU activation, which involved induction of pAkt and pERK1/2 activation that confer DDP resistance in immunocompromised mice and alteration of this balance, allows sensitization to the antitumor activity of cisplatin chemotherapy.

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Expression of clusterin, pERK1/2, and pAKT in A549DDPtumor tissue from the mice (A, B, C). A549, A549DDP, A549DDP/sCLU shRNA, and A549DDP/shRNA cells were injected subcutaneously into the right flank of nude mice. Three weeks later, DDP (4 mg/kg body/wt.,i.p) was administered i.v. once every 3 days. The treatments lasted for 15 days. Protein expression in the xenograft tumor was visualized with the indicated antibodies.
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Fig3: Expression of clusterin, pERK1/2, and pAKT in A549DDPtumor tissue from the mice (A, B, C). A549, A549DDP, A549DDP/sCLU shRNA, and A549DDP/shRNA cells were injected subcutaneously into the right flank of nude mice. Three weeks later, DDP (4 mg/kg body/wt.,i.p) was administered i.v. once every 3 days. The treatments lasted for 15 days. Protein expression in the xenograft tumor was visualized with the indicated antibodies.

Mentions: Western blot indicated that the expression of clusterin, pAKT, and pERK1/2 in A549 solid tumors was weak, while it was rich in the DDP-treated A549 solid tumors (Figure 3A). In the A549DDP solid tumor, the expression of clusterin, pAKT, and pERK1/2 in A549 solid tumors was very rich; however, in the DDP-treated A549DDP solid tumors, no apparent increase of clusterin, pAKT, and pERK1/2 expression was found (Figure 3B). In the A549DDP/sCLU shRNA solid tumor, the expression of clusterin, pAKT, and pERK1/2 in A549 solid tumors was very weak; furthermore, in the DDP-treated A549DDP/sCLU shRNA solid tumors, the clusterin, pAKT, and pERK1/2 expression was also very weak (Figure 3C).Figure 3


sCLU regulates cisplatin chemosensitivity of lung cancer cells in vivo.

Ma G, Cai H, Gao L, Wang M, Wang H - World J Surg Oncol (2015)

Expression of clusterin, pERK1/2, and pAKT in A549DDPtumor tissue from the mice (A, B, C). A549, A549DDP, A549DDP/sCLU shRNA, and A549DDP/shRNA cells were injected subcutaneously into the right flank of nude mice. Three weeks later, DDP (4 mg/kg body/wt.,i.p) was administered i.v. once every 3 days. The treatments lasted for 15 days. Protein expression in the xenograft tumor was visualized with the indicated antibodies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4358856&req=5

Fig3: Expression of clusterin, pERK1/2, and pAKT in A549DDPtumor tissue from the mice (A, B, C). A549, A549DDP, A549DDP/sCLU shRNA, and A549DDP/shRNA cells were injected subcutaneously into the right flank of nude mice. Three weeks later, DDP (4 mg/kg body/wt.,i.p) was administered i.v. once every 3 days. The treatments lasted for 15 days. Protein expression in the xenograft tumor was visualized with the indicated antibodies.
Mentions: Western blot indicated that the expression of clusterin, pAKT, and pERK1/2 in A549 solid tumors was weak, while it was rich in the DDP-treated A549 solid tumors (Figure 3A). In the A549DDP solid tumor, the expression of clusterin, pAKT, and pERK1/2 in A549 solid tumors was very rich; however, in the DDP-treated A549DDP solid tumors, no apparent increase of clusterin, pAKT, and pERK1/2 expression was found (Figure 3B). In the A549DDP/sCLU shRNA solid tumor, the expression of clusterin, pAKT, and pERK1/2 in A549 solid tumors was very weak; furthermore, in the DDP-treated A549DDP/sCLU shRNA solid tumors, the clusterin, pAKT, and pERK1/2 expression was also very weak (Figure 3C).Figure 3

Bottom Line: The effect of sCLU silencing or overexpression on pAkt and pERK1/2 expression and chemosensitivity in vivo was detected by Western blot assay.The results showed sCLU silencing increased the chemosensitivity of A549(DDP) cells to DDP in vivo via downregulation of pAkt and pERK1/2 expression.And sCLU overexpression decreased the chemosensitivity of A549 cells to DDP in vivo via upregulation of pAkt and pERK1/2 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Lab, People's Hospital of Laiwu, Laiwu, China. maguoliang7782@sina.com.

ABSTRACT

Background: In a previous analysis using a lung cancer cell line model, we have found that therapies directed against secreted clusterin (sCLU) and its downstream signaling targets pAkt and pERK1/2 may have the potential to enhance the efficacy of cisplatin (DDP)-based chemotherapy in vitro. Here, we investigated the therapies directed against sCLU on the DDP-based chemotherapy in vivo and explored the mechanism.

Methods: Using lung cancer cell lines, A549 cells and DDP-resistant A549 cells (A549(DDP)), we determined the effect of sCLU silencing using short interfering double-stranded RNA (siRNA) on chemosensitivity in immunocompromised mice bearing A549(DDP) tumors. We then determined the effect of sCLU overexpression via stable sCLU transfection on chemosensitivity in immunocompromised mice bearing A549 tumors. The effect of sCLU silencing or overexpression on pAkt and pERK1/2 expression and chemosensitivity in vivo was detected by Western blot assay.

Results: The results showed sCLU silencing increased the chemosensitivity of A549(DDP) cells to DDP in vivo via downregulation of pAkt and pERK1/2 expression. And sCLU overexpression decreased the chemosensitivity of A549 cells to DDP in vivo via upregulation of pAkt and pERK1/2 expression.

Conclusions: We therefore concluded that the DDP-induced sCLU activation, which involved induction of pAkt and pERK1/2 activation that confer DDP resistance in immunocompromised mice and alteration of this balance, allows sensitization to the antitumor activity of cisplatin chemotherapy.

Show MeSH
Related in: MedlinePlus