Table 5 Cellular models demonstrating the importance of UPR in cancer chemotherapy resistance

From: Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers

Tumor origin

Materials

Chemotherapy

Methods

GRP78

IRE1α

XBP1

XBP1s

ATF6

PERK

eIF2α

ATF4

Others

Comments

Ref.

Bladder

T24/83

Etoposide, doxorubicin, camptothecin

WB

+

        

Associated with resistance to apoptosis

116

Bone

MG-63, SaOS-2

Cisplatin

WB

+

       

(1)

Associated with resistance to apoptosis

117

Brain

U87

Temozolomide

WB

+

        

Increased with ER stress (DTT)

46

 

U87 and U251

Temozolomide

WB

+

       

(1)

 

47

 

LN229

Temozolomide, camptothecin, 5-FU

WB

+

        

Associated with resistance to apoptosis

47

 

A172 and LNZ308

Etoposide, cisplatin

IHC

+

        

Associated with resistance to apoptosis

48

 

U87 and U251

Temozolomide

     

+

  

+

(2)

Associated with radicol-induced apoptosis

118

Breast

MCF-7

Doxorubicin

WB

+

       

(3)

 

119

 

T47D

Estrogen

Q-PCR, WB

+

  

+

   

+

(4)

 

52

 

MCF-7

Estrogen

Q-PCR, WB

+

+

+

+

+

+

+

 

(5)

 

52

 

MCF-7 xenograft

Estrogen

Q-PCR

+

+

+

 

(6)

 

52

 

293T, MCF-7

Etoposide

WB

+

        

Associated with BIK interaction

120

 

MCF-7, T47D

Fulvestrant

WB

  

+

+

      

121

 

LCC1, LCC9

Fulvestrant

WB

+

  

+

   

+

(7)

Associated with autophagy

122

 

LCC9, MCF-7

Fulvestrant

WB

  

+

+

     

Associated with resistance to apoptosis

123

 

MDA-M35, T47D, MCF-7

Quercetin

Q-PCR, WB

+

   

+

   

(8)

 

124

 

MCF-7

Paclitaxel

WB

+

        

Associated with resistance to apoptosis

125

 

T47D

Tamoxifen

WB

+

         

51

 

MCF-7, T47D

MCF-7 xenograft

Tamoxifen

Tamoxifen

RT–PCR, WB

WB

   

+

+

    

(9)

Decreased resistance with IRE1 inhibitor

decreased with IRE1 inhibitor

53

 

MCF-7, T47D

Tamoxifen

WB

  

+

+

      

121

 

MCF-7 xenograft

Tamoxifen

WB

  

+

+

      

121

 

Rat DMBA-induced mammary tumors

Tamoxifen

WB

+

+

     

+

(1)

Associated with autophagy

126

 

SKBr3

Trastuzumab

Q-PCR, ELISA

+

       

(10)

Increased with ER stress (Tg)

127

Cervix

SiHa-derived stem-like cells

Cisplatin

RT–PCR, WB

+

  

+

    

(11)

increased apoptosis with IRE1 inhibitor

128

Colorectal

Colo205, HCT116, SW480, SW626

Cisplatin, 5-FU

WB

+

        

Associated with resistance to apoptosis

54

 

HCT116

HT29

5-FU

         

(12)

Associated with resistance to apoptosis

57

Kidney

A498, ACHN

Doxorubicin, 5-FU

IHC

+

        

Associated to cell cycle control

71

Liver

HepG2

Doxorubicin

RT–PCR, WB

+

        

Increased survival under glucose privation

60

 

7741, HepG2 and 7741 xenograft

Doxorubicin, VP-16

IHC, WB

+

        

Correlated with CD147 expression

62

 

HepG2, MHCC97

Sorafenib

    

+

    

(9)

Associated with resistance to apoptosis-dependent of RACK expression

72

Lung

PC13, PC14

Doxorubicin

WB

+

        

Associated with resistance to apoptosis

64

Ovary

PEO4

Estrogen

Q-PCR, WB

+

  

+

      

52

 

OVCAR-3

Paclitaxel

WB

+

        

Associated with resistance to apoptosis

125

Skin

Hep3 (dormant versus tumorigene)

Etoposide, doxorubicin

Q-PCR, WB

+

       

(13)

Associated with resistance to apoptosis

129

Others

CHO (hamster)

Etoposide, doxorubicin, camptothecin

WB

+

        

Associated with resistance to apoptosis

116

 

CHO (hamster)

Etoposide

WB

+

        

Increased under ER stress (tg)

130

 

NIH3T3

Etoposide

WB

+

        

Increased under ER stress (tg)

130

  1. Abbreviations: ATF, activating transcription factor; BIK, Bcl-2-interacting killer; DTT, dithiothreitol; eIF2α, eukaryotic initiation factor 2α; ERO1L, ER oxidoreduction 1-like; 5-FU, 5-fluorouracil; FRP, glucose-regulated protein; HSP, heat-shock protein; IHC, immunohistochemistry; IRE1α, inositol requiring enzyme 1α; JNK, c-Jun N-terminal protein kinase; LCN2, lipocalin 2; PDI, protein disulfide isomerase; PERK, PKR-like endoplasmic reticulum kinase; Q-PCR, quantitative PCR; RT–PCR, reverse transcriptase–PCR; Tg, thapsigargin; UPR, unfolded protein response; WB, western blot; XBP, X-box binding protein.
  2. (1) CHOP(+).
  3. (2) calnexin(+), calreticulin(+), CHOP(+), GRP94(+), PDI(−), phosphorylated IRE1α, PERK and eIF2α(+).
  4. (3) CHOP(+), phosphorylated PERK.
  5. (4) Decreased CHOP, cleaved ATF6, phosphorylated PERK and eIF2α.
  6. (5) DNAJC3, ERO1LB, GRP94.
  7. (6) CHOP(+), DNAJC3(−), ERO1Lb(−), GADD34(+).
  8. (7) CHOP(+), GRP94(+), cleaved ATF6, phosphorylated eIF2α.
  9. (8) CHOP(+), phosphorylated eIF2α and JNK.
  10. (9) Phosphorylated IRE1α.
  11. (10) CHOP(+), LCN2(+).
  12. (11) Phosphorylated eIF2α.
  13. (12) Calnexin(+).
  14. (13) HSP47(+), PDI(+), phosphorylated PERK and eIF2.