Antisense oligodeoxynucleotide targeting HER2 mRNA sensitized docetaxel in breast cancer treatment

Figures & data

Table

HER2	Forward	5′-CAATGGAGACCCGCTGAAC-3′
	Reverse	5′-CAGTGCGCGTCAGGCTCT-3′
G3PDH	Forward	5′-ACCACAGTCCATGCCATCAC-3′
	Reverse	5′-TCCACCACCCTGTTGCTGTA-3′

Table

HA6722	5′-CAGCAGCCGAGCCAGCCCGA-3′
Scramble6722	5′-ACAGCAGCCGAGCCAGCCCG-3′

Figure 1.  HA6722 enhanced the inhibitory effects of Docetaxel (TXT) on growth of SK-BR-3 cell lines. Cells were either transfected with HA6722/scramble6722 alone (b), treated with various concentrations of TXT alone (a), or had the combination treatment (c), for 24 h before the MTT assay was performed. Each experiment was carried out three times independently, and each assay was performed in six replicate wells. Inhibition rate was calculated as the ratio of the mean absorbance of treated cells to that of control cells.

Figure 2.  Reverse transcription polymerase chain reaction (RT-PCR) demonstrating the down-regulation of HER2 mRNA by HA6722. (A) SK-BR-3 cells were transfected with various amounts of HA6722 for 24 h before the mRNA expression was evaluated. (B) SK-BR-3 cells were either transfected with Scramble6722, a random oligonucleotide (random), 200 nM HA6722 for 9 h or not transfected (baseline) before the mRNA evaluation via RT-PCR. The house-keeping gene GAPDH was used as an internal control.

Figure 3.  Down-regulation of HER2 by HA6722 in vivo. Each treatment group was consisted of seven mice. Tumors from those mice surviving the entire treatment period were excised and photographed. (A) Blank group; (B) T (M) group; (C) TScr (M) group; (D) HA (M) group; (E) THA (M) group.

Figure 4.  Effects of HA6722 on tumor volume and tumor weight in the nude mouse model. Each treatment group consisted of seven mice. (A) HA6722 alone (M, medium dosage, 5 mg/kg/day) could inhibit tumor growth (P < 0.05 compared with blank treatment). THA (L), docetaxel (TXT) 7.5 mg/kg/day + HA6722 2 mg/kg/day; (B) HA6722 sensitized TXT on tumor growth. Inhibitory effect of TXT (medium dosage, 7.5 mg/kg/day) plus HA6722 (5 mg/kg/day) was comparable with that of high TXT dosage treatment [T (H), 15 mg/kg/day]. [P < 0.05 compared with blank treatment, P > 0.05 between T (H) and THA (M) groups]; (C) final tumor weights of different treatment groups compared with blank treatment *P < 0.01; **P < 0.01; ***P < 0.05; ^#P < 0.05.