Limits...
Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers.

Kim JH, Park JM, Roh YJ, Kim IW, Hasan T, Choi MG - BMC Cancer (2015)

Bottom Line: Pretreatment with a ABCG2 inhibitor, Ko-143, significantly enhanced the PDT efficacy in HT29 cells compared to vehicle-pretreated cells.Furthermore, SW480/ABCG2 cells showed significantly decreased PDT effect compared to the control cells.The increased or decreased cell survival was significantly correlated with the production level of singlet oxygen after PDT.

View Article: PubMed Central - PubMed

Affiliation: Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. jhsubzero@naver.com.

ABSTRACT

Background: Photodynamic therapy (PDT) contains a photosensitizing process, which includes cellular uptake of photosensitizer and delivery of light to the target. ATP-binding cassette subfamily G2 (ABCG2) regulates endogenous protoporphyrin levels. In human colon cancers, it is not fully examined the role of ABCG2 in porphyrin-based photodynamic therapy.

Methods: SW480 and HT29 cells were selected because they showed low and high ABCG2 expression levels, respectively. Pyropheophorbid-a (PPa) was used as a photosensitizer. Cells were exposed to a 670 nm diod laser. Cell viability and necrosi apoptosis was examined. Production level of singlet oxygen was detected with the photomultiplier-tube s/ -based singlet oxygen detection system.

Results: SW480 cells, which expressed lower level of ABCG2, showed the higher uptake of PPa than HT-29 cells. The uptake level of PPa was significantly correlated with the decreased cell viability after PDT. Pretreatment with a ABCG2 inhibitor, Ko-143, significantly enhanced the PDT efficacy in HT29 cells compared to vehicle-pretreated cells. To confirm the ABCG2 effect on PDT, we established ABCG2 over-expressing stable cells in SW480 cells (SW480/ABCG2). Furthermore, SW480/ABCG2 cells showed significantly decreased PDT effect compared to the control cells. The increased or decreased cell survival was significantly correlated with the production level of singlet oxygen after PDT.

Conclusion: ABCG2 plays an important role in determining the PDT efficacy by controlling the photosensitizer efflux rate. This implies the control of ABCG2 expression may be a potential solution to enhance photosensitivity.

No MeSH data available.


Related in: MedlinePlus

Antitumor effects of PDT in in vivo experiments. a, SW480 and SW480/ABCG2 cells were collected and subcutaneously injected into BALB/c nude mice. The sizes of tumors were measured using a caliper, tumor volume was calculated using the formula: 0.523 × length × width2 (mm3). b, HT-29 cells xenografted in nude mouse were treated with PBS alone, PPa + irradiation with or without Ko-143 pretreatment. Combined treatment of PPa with Ko-143 enhanced the sensitivity of HT29 cell to PDT. Data are means ± SEM from n = 4 (*P < 0.05, **P < 0.01, #P < 0.0001)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4494642&req=5

Fig6: Antitumor effects of PDT in in vivo experiments. a, SW480 and SW480/ABCG2 cells were collected and subcutaneously injected into BALB/c nude mice. The sizes of tumors were measured using a caliper, tumor volume was calculated using the formula: 0.523 × length × width2 (mm3). b, HT-29 cells xenografted in nude mouse were treated with PBS alone, PPa + irradiation with or without Ko-143 pretreatment. Combined treatment of PPa with Ko-143 enhanced the sensitivity of HT29 cell to PDT. Data are means ± SEM from n = 4 (*P < 0.05, **P < 0.01, #P < 0.0001)

Mentions: To test for the effects of ABCG2 expression in vivo, PDT was applied to xenograft tumor models established by subcutaneous injection of colon cancer cells (SW480, SW480/ABCG2). When tumor size reached150-200 mm3, PPa was administered to the tumors at the dose of 1.25 mg/kg followed by irradiation with a 670 nm diode light (150 J/cm2) 6 h later. There was no change in size of the tumor between SW480 and SW480/ABCG2 injected mice immediately after PDT. However, at 7 days after the injection, the tumor volume increased by a greater extent in mice injected with SW480/ABCG2 cells compared to mice injected with SW480 cells (Fig. 6a). To confirm this result, HT-29 cells xenografted in nude mouse were treated with PBS alone, PPa + irradiation with or without Ko-143 pretreatment (Fig. 6b). As shown in cell experiments, combined treatment of PPa with Ko-143 enhanced the sensitivity of HT29 cell to PDT. These results show that ABCG2 expression influences the outcome of PDT in vivo.Fig. 6


Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers.

Kim JH, Park JM, Roh YJ, Kim IW, Hasan T, Choi MG - BMC Cancer (2015)

Antitumor effects of PDT in in vivo experiments. a, SW480 and SW480/ABCG2 cells were collected and subcutaneously injected into BALB/c nude mice. The sizes of tumors were measured using a caliper, tumor volume was calculated using the formula: 0.523 × length × width2 (mm3). b, HT-29 cells xenografted in nude mouse were treated with PBS alone, PPa + irradiation with or without Ko-143 pretreatment. Combined treatment of PPa with Ko-143 enhanced the sensitivity of HT29 cell to PDT. Data are means ± SEM from n = 4 (*P < 0.05, **P < 0.01, #P < 0.0001)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4494642&req=5

Fig6: Antitumor effects of PDT in in vivo experiments. a, SW480 and SW480/ABCG2 cells were collected and subcutaneously injected into BALB/c nude mice. The sizes of tumors were measured using a caliper, tumor volume was calculated using the formula: 0.523 × length × width2 (mm3). b, HT-29 cells xenografted in nude mouse were treated with PBS alone, PPa + irradiation with or without Ko-143 pretreatment. Combined treatment of PPa with Ko-143 enhanced the sensitivity of HT29 cell to PDT. Data are means ± SEM from n = 4 (*P < 0.05, **P < 0.01, #P < 0.0001)
Mentions: To test for the effects of ABCG2 expression in vivo, PDT was applied to xenograft tumor models established by subcutaneous injection of colon cancer cells (SW480, SW480/ABCG2). When tumor size reached150-200 mm3, PPa was administered to the tumors at the dose of 1.25 mg/kg followed by irradiation with a 670 nm diode light (150 J/cm2) 6 h later. There was no change in size of the tumor between SW480 and SW480/ABCG2 injected mice immediately after PDT. However, at 7 days after the injection, the tumor volume increased by a greater extent in mice injected with SW480/ABCG2 cells compared to mice injected with SW480 cells (Fig. 6a). To confirm this result, HT-29 cells xenografted in nude mouse were treated with PBS alone, PPa + irradiation with or without Ko-143 pretreatment (Fig. 6b). As shown in cell experiments, combined treatment of PPa with Ko-143 enhanced the sensitivity of HT29 cell to PDT. These results show that ABCG2 expression influences the outcome of PDT in vivo.Fig. 6

Bottom Line: Pretreatment with a ABCG2 inhibitor, Ko-143, significantly enhanced the PDT efficacy in HT29 cells compared to vehicle-pretreated cells.Furthermore, SW480/ABCG2 cells showed significantly decreased PDT effect compared to the control cells.The increased or decreased cell survival was significantly correlated with the production level of singlet oxygen after PDT.

View Article: PubMed Central - PubMed

Affiliation: Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. jhsubzero@naver.com.

ABSTRACT

Background: Photodynamic therapy (PDT) contains a photosensitizing process, which includes cellular uptake of photosensitizer and delivery of light to the target. ATP-binding cassette subfamily G2 (ABCG2) regulates endogenous protoporphyrin levels. In human colon cancers, it is not fully examined the role of ABCG2 in porphyrin-based photodynamic therapy.

Methods: SW480 and HT29 cells were selected because they showed low and high ABCG2 expression levels, respectively. Pyropheophorbid-a (PPa) was used as a photosensitizer. Cells were exposed to a 670 nm diod laser. Cell viability and necrosi apoptosis was examined. Production level of singlet oxygen was detected with the photomultiplier-tube s/ -based singlet oxygen detection system.

Results: SW480 cells, which expressed lower level of ABCG2, showed the higher uptake of PPa than HT-29 cells. The uptake level of PPa was significantly correlated with the decreased cell viability after PDT. Pretreatment with a ABCG2 inhibitor, Ko-143, significantly enhanced the PDT efficacy in HT29 cells compared to vehicle-pretreated cells. To confirm the ABCG2 effect on PDT, we established ABCG2 over-expressing stable cells in SW480 cells (SW480/ABCG2). Furthermore, SW480/ABCG2 cells showed significantly decreased PDT effect compared to the control cells. The increased or decreased cell survival was significantly correlated with the production level of singlet oxygen after PDT.

Conclusion: ABCG2 plays an important role in determining the PDT efficacy by controlling the photosensitizer efflux rate. This implies the control of ABCG2 expression may be a potential solution to enhance photosensitivity.

No MeSH data available.


Related in: MedlinePlus