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. 2008 Feb 6;99(2):316–323. doi: 10.1111/j.1349-7006.2007.00690.x

Figure 5.

Figure 5

Antisense oligonucleotide study in prostate tumors transplanted onto cranial bone and into the subcutis of male rats. (a) Expression of transforming growth factor β receptor 1 (TGFβR1) at the tumor–bone (TB) interface treated with vehicle control (VC), TGFβR1 antisense oligonucleotide; TGFβR1‐ASO(1), TGFβR1‐ASO(2), TGFβR1‐ASO(3), random control oligonucleotide RCO(1) and RCO(2) shown by quantitative reverse transcription–polymerase chain reaction and Western blot analysis. Because TGFβR1‐ASO(1) exerted the most suppressive effect on TGFβR1 expression, we subsequently chose TGFβR1‐ASO(1) as ‘TGFβR1‐ASO’ and RCO(1) as ‘RCO’. (b) Tumor volume curves. Cranial tumor volume in VC and RCO groups shows a rapid increase, and the TGFβR1‐ASO group shows a gradual increase (n = 3 in each group). (c) Bone destruction at the TB‐interface. The dotted line indicates bone destruction. Quantitative analysis of the bone destruction index revealed that TGFβR1‐ASO significantly reduced bone destruction ratio (right). HE, hematoxylin–eosin. (Magnification: ×20). (d) Tartrate‐resistant acid phosphatase (TRAP) staining at the TB‐interface. Quantitative analysis indicated that TGFβR1‐ASO significantly reduced TRAP‐positive multinucleated cells (right) (magnification: ×100). (e) Osteoblasts at the TB‐interface. Many osteoblasts were observed in the woven bone at the TB‐interface in the RCO group (left) and less osteoblasts in the TGFβR1‐ASO group (middle). TGFβR1‐ASO treatment significantly reduced osteoblasts at the TB‐interface (right) (magnification: ×100). (f) Immunohistochemical staining of proliferating cell nuclear antigen (PCNA). Many PCNA‐positive cells were observed at the TB‐interface in the RCO group (left) and less numbers in the TGFβR1‐ASO group (middle). TGFβR1‐ASO treatment significantly suppressed PCNA index at the TB‐interface, but not at the non‐TB (NTB) interface (right) (magnification: ×100). (g) Immunohistochemical staining of phosphorylated Smad2 (pSmad2). Many positive cells were observed in the TB‐interface of RCO (left) and less in TGFβR1‐ASO (middle). The index of pSmad2‐positive cells at the TB‐interface revealed that TGFβR1‐ASO reduced TGFβ signaling, but that VC and RCO did not. No significant difference was observed at the NTB‐interface (right) (magnification: ×100). *P < 0.05; **P < 0.01; ***P < 0.001.