Limits...
The effect of radiation exposure on multidrug resistance: in vitro and in vivo studies using non-small lung cancer cells.

Kanno S, Utsunomiya K, Kono Y, Tanigawa N, Sawada S - EJNMMI Res (2015)

Bottom Line: In vivo, fluorescence photon counts were significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after administration of doxorubicin, as compared to the not-irradiated mice.However, the C in/C out ratio in the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0 groups.In combination with a low-dose MDR modulator, GG918, MDR transport function was synergistically reduced 48 h post-irradiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, 573-1010 Osaka Japan.

ABSTRACT

Background: Technetium-99m methoxyisobutylisonitrile (Tc MIBI) is a substrate with the same uptake kinetics as doxorubicin. Multidrug resistance (MDR) is a mechanism that impedes chemotherapy of non-small cell lung cancer (NSCLC). We examined the effect of radiation exposure on MDR in NSCLC and the synergy between an MDR modulator, GG918, and radiation, using (99m)Tc MIBI in vitro and doxorubicin in vivo.

Methods: In vitro NSCLC cells (H1299) were exposed to radiation (3-, 6-, and 9-Gy-irradiated groups) alongside a not-irradiated (0 Gy) group. Technetium-99 metastable methoxyisobutylisonitrile ((99m)Tc MIBI) was administered to cell suspensions at 48 h after irradiation. Cell radioactivity was measured, and C in/C out ratios were calculated and compared. NSCLC cells were also subcutaneously transplanted into the left thigh of nude mice, which were subsequently raised for 2 weeks. Two groups of mice were used: mice exposed to irradiation (9-Gy-irradiated) and those that were not (not-irradiated). Doxorubicin was administered through the caudal vein at 48 h after the irradiation. Using an in vivo imaging system, intratumoural photon counts were measured. To determine the synergy between the MDR modulator and 3- or 6-Gy irradiation, the final GG918 concentration was determined: 0.1 μM (N-H, 3-H, and 6-H groups), 0.001 μM (N-L, 3-L, and 6-L groups), and 0 μM (N-0, 3-0, and 6-0 groups). C in/C out ratios were calculated and compared among the groups.

Results: C in/C out after 6- or 9-Gy irradiation was significantly higher than that of the not-irradiated group (0 Gy). In vivo, fluorescence photon counts were significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after administration of doxorubicin, as compared to the not-irradiated mice. The C in/C out ratio in the N-H, 3-H, and 6-H groups was significantly higher than that in the N-0, 3-0, and 6-0 groups. There was no significant difference between C in/C out in the N-L group and that of the N-0 group. However, the C in/C out ratio in the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0 groups.

Conclusions: Irradiation decreased MDR in NSCLC cells. In combination with a low-dose MDR modulator, GG918, MDR transport function was synergistically reduced 48 h post-irradiation.

No MeSH data available.


Related in: MedlinePlus

The immunocytochemistrical expression of Pgp and BCRP. The immunocytochemistrical expression of Pgp and BCRP was positive, the proportion score (PS) 5/5 + the intensity score (IS) 3/3 = total score 8/8, localizing these proteins to the cell membrane of the not-irradiated tumour cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4385263&req=5

Fig2: The immunocytochemistrical expression of Pgp and BCRP. The immunocytochemistrical expression of Pgp and BCRP was positive, the proportion score (PS) 5/5 + the intensity score (IS) 3/3 = total score 8/8, localizing these proteins to the cell membrane of the not-irradiated tumour cells.

Mentions: Immunodetection of Pgp and BCRP was positive, with these proteins localized in the membranes of H1299 cells (Figures 2 and 3). In the not-irradiated cells shown in Figure 2, the expression of Pgp and BCRP were as follows: PS 5 + IS 3 = 8. There was no change after 9-Gy irradiation, followed by 48 h of culturing, as shown for the cells in Figure 3, with both Pgp and BCRP being PS 5 + IS 3 = 8.Figure 2


The effect of radiation exposure on multidrug resistance: in vitro and in vivo studies using non-small lung cancer cells.

Kanno S, Utsunomiya K, Kono Y, Tanigawa N, Sawada S - EJNMMI Res (2015)

The immunocytochemistrical expression of Pgp and BCRP. The immunocytochemistrical expression of Pgp and BCRP was positive, the proportion score (PS) 5/5 + the intensity score (IS) 3/3 = total score 8/8, localizing these proteins to the cell membrane of the not-irradiated tumour cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385263&req=5

Fig2: The immunocytochemistrical expression of Pgp and BCRP. The immunocytochemistrical expression of Pgp and BCRP was positive, the proportion score (PS) 5/5 + the intensity score (IS) 3/3 = total score 8/8, localizing these proteins to the cell membrane of the not-irradiated tumour cells.
Mentions: Immunodetection of Pgp and BCRP was positive, with these proteins localized in the membranes of H1299 cells (Figures 2 and 3). In the not-irradiated cells shown in Figure 2, the expression of Pgp and BCRP were as follows: PS 5 + IS 3 = 8. There was no change after 9-Gy irradiation, followed by 48 h of culturing, as shown for the cells in Figure 3, with both Pgp and BCRP being PS 5 + IS 3 = 8.Figure 2

Bottom Line: In vivo, fluorescence photon counts were significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after administration of doxorubicin, as compared to the not-irradiated mice.However, the C in/C out ratio in the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0 groups.In combination with a low-dose MDR modulator, GG918, MDR transport function was synergistically reduced 48 h post-irradiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, 573-1010 Osaka Japan.

ABSTRACT

Background: Technetium-99m methoxyisobutylisonitrile (Tc MIBI) is a substrate with the same uptake kinetics as doxorubicin. Multidrug resistance (MDR) is a mechanism that impedes chemotherapy of non-small cell lung cancer (NSCLC). We examined the effect of radiation exposure on MDR in NSCLC and the synergy between an MDR modulator, GG918, and radiation, using (99m)Tc MIBI in vitro and doxorubicin in vivo.

Methods: In vitro NSCLC cells (H1299) were exposed to radiation (3-, 6-, and 9-Gy-irradiated groups) alongside a not-irradiated (0 Gy) group. Technetium-99 metastable methoxyisobutylisonitrile ((99m)Tc MIBI) was administered to cell suspensions at 48 h after irradiation. Cell radioactivity was measured, and C in/C out ratios were calculated and compared. NSCLC cells were also subcutaneously transplanted into the left thigh of nude mice, which were subsequently raised for 2 weeks. Two groups of mice were used: mice exposed to irradiation (9-Gy-irradiated) and those that were not (not-irradiated). Doxorubicin was administered through the caudal vein at 48 h after the irradiation. Using an in vivo imaging system, intratumoural photon counts were measured. To determine the synergy between the MDR modulator and 3- or 6-Gy irradiation, the final GG918 concentration was determined: 0.1 μM (N-H, 3-H, and 6-H groups), 0.001 μM (N-L, 3-L, and 6-L groups), and 0 μM (N-0, 3-0, and 6-0 groups). C in/C out ratios were calculated and compared among the groups.

Results: C in/C out after 6- or 9-Gy irradiation was significantly higher than that of the not-irradiated group (0 Gy). In vivo, fluorescence photon counts were significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after administration of doxorubicin, as compared to the not-irradiated mice. The C in/C out ratio in the N-H, 3-H, and 6-H groups was significantly higher than that in the N-0, 3-0, and 6-0 groups. There was no significant difference between C in/C out in the N-L group and that of the N-0 group. However, the C in/C out ratio in the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0 groups.

Conclusions: Irradiation decreased MDR in NSCLC cells. In combination with a low-dose MDR modulator, GG918, MDR transport function was synergistically reduced 48 h post-irradiation.

No MeSH data available.


Related in: MedlinePlus