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. 2009 Jun 5;14(6b):1777–1792. doi: 10.1111/j.1582-4934.2009.00795.x

Fig 3.

Fig 3

Selective inhibition of IGF-IR induces negative biological effects in CML cell lines. (A) The selective inhibitor of IGF-IR PPP induces concentration- and time-dependent decrease in the viability of CML cell lines. Results shown are the means ± S.D. of three consistent experiments (24 hrs in the left panel and 48 hrs in the right panel). The effect of PPP is more pronounced in the KBM-5 and MEG01 cell lines. At 24 hrs, the decrease in cell viability was statistically significant between the four cell lines and the control cells AG01523 (P < 0.0001). At 48 hrs, the decrease in the cell viability remained statistically significant between the four cell lines and the control cells AG01523, albeit more significant in KBM-5 and MEG01 cells (P= 0.017 for K562 and BV173 and P < 0.0001 for KBM-5 and MEG01). In addition, the difference in PPP-induced decrease in cell viability between both K562 and BV173 cell lines versus KBM-5 and MEG01 was statistically significant (P < 0.0001 at both 24 and 48 hrs). (B) Antagonism of IGF-IR by PPP induces concentration- and time-dependent increase in apoptotic cell death in CML cell lines (results collected at 24 hrs are shown in the left panel and at 48 hrs in the right panel). Results shown represent the means ± S.D. of three consistent experiments. *: P < 0.05, †: P < 0.01, and ‡: P < 0.001 compared with control untreated cells. At 24 hrs, the cell line MEG01 demonstrated significantly more apoptotic cell death compared with the other three cell lines. After 48 hrs, apoptosis was more pronounced in KBM-5 and MEG01. Comparing the collective response of K562 and BV173 to PPP versus KBM-5 and MEG01 cell lines showed that P= 0.0021 at 24 hrs and P= 0.0004 at 48 hrs. (C) Treatment of CML cell lines with PPP induces G2/M-phase cell cycle arrest as demonstrated by flow cytometric analysis after staining with PI. (D) Morphological changes consistent with apoptosis are shown, and include nuclear condensation and fragmentation and cell shrinkage (black arrowheads). Markedly increased atypical mitotic forms are consistent with G2/M-phase cell cycle (red arrowheads). Original magnification is ×500. (E) Antagonism of IGF-IR signalling by PPP induces concentration-dependent decrease in the proliferation of CML cell lines at 24 hrs. At a PPP concentration of 1.0 μm, this effect is less pronounced in the BV173 cell line. The results shown are the means ± S.D. of three experiments. *: P < 0.001 compared with control untreated cells and †: P < 0.001 compared with PPP (0.2 μM). (F) Treatment of CML cell lines with PPP markedly decreases their growth in soft agar. The effect is more prominent in K562, KBM-5 and MEG01. The means ± S.D. of the numbers of the colonies of each cell line from three consistent experiments are shown in the left panel. *: P < 0.01 and †: P <0.001 compared with control untreated cells. Representative cell culture plates from K562 and KBM-5 cells are depicted in the right panel.