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Figure 6 | BMC Cancer

Figure 6

From: Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

Figure 6

In vivo mechanism of antitumor activity of rapamycin and bortezomib in xenograft model. (A) Ex vivo immunohistochemistry staining of Akt, p-Akt, PCNA, CD31 or TUNEL in HCCLM3-R xenografts (magnification, ×200). The staining of p-Akt was increased in rapamycin-treated tumors, but inhibited in bortezomib- or the combination-treated tumors. (B) The increase of p-Akt in rapamycin-treated tumors and the decrease in bortezomib-treated tumors were also observed by Western blot analysis. Rapamycin-induced Akt phosphorylation was abrogated by bortezomib in the combination-treated tumors. (A, C) Quantitation of PCNA positive cells demonstrated that rapamycin or bortezomib significantly inhibited tumor growth, as compared with control (* P < 0.05), which was markedly enhanced by the combination of both agents (** P < 0.01, versus control group and P < 0.01 versus monotherapy). (A, D) The average number of CD31-positive vessels was significantly reduced in tumors from the rapamycin monotherapy group (* P < 0.05, versus control group), which was further enhanced by the combined therapy of rapamycin and bortezomib (** P < 0.01, versus control group; and # P < 0.05, versus rapamycin group). (A, E) The number of TUNEL-positive cells in tumors was significantly elevated in bortezomib treatment group (** P < 0.01, versus control group) and the combined treatment group (** P < 0.01, versus control group or rapamycin group).

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